Seasonal changes in amino acids and phenolic compounds in fruits from hybrid cross populations of American grapes differing in disease resistance.

The production of wine grapes in upstate New York (USA) is limited by diseases that are promoted by the cool and sometimes rainy climate. A breeding program has been introducing disease resistance from related species into the cultivated stock. Previous work has indicated that such resistance may be based on biochemical reactions rather than on a hypersensitive reaction. We therefore undertook metabolic profiling of amino acids and phenolic compounds in berries from collections of susceptible and resistant hybrids over the course of berry development to determine whether any of these compounds could be causal in disease resistance. The most abundant amino acids were GLN, ARG, PRO and THR. The amount of amino acids in ripe berries was from 3 to 4.7-fold higher compared to earlier stages. The concentrations of total phenolics were variable through the season with no consistent trend between susceptible and resistant fruits. Notable changes in phenolic compounds, especially anthocyanins, were recorded, especially during the ripening phase, when phenolics and anthocyanins increased following veraison. The most abundant phenolic compounds were catechin and epi-catechin; the most abundant anthocyanin was delphinidin-3-glucoside, which had a slightly greater concentration in resistant fruit at harvest, followed by malvidin-3-glucoside and petunidin-3-glucoside. The content of both amino acids and phenolic compounds in white-fruited parent cv. Horizon was equal to several-fold lower than the progeny plants, whether susceptible or resistant, depending on the harvest time. While no major differences between susceptible and resistant lines were found, multivariate analyses showed that it is possible to discriminate the susceptibility or resistance of grapes by analyzing their combined concentrations of amino acids, polyphenols and anthocyanins. Therefore, these compounds are influenced by the resistance capacity of grapes and could be used as a chemical fingerprint of this ability. However, it is likely that these are associations with disease resistance rather than their cause as no major consistent differences were noted.

Hybridization improved bacteria resistance in abalone: Evidence from physiological and molecular responses.

Hybridization is an effective way of improving germplasm in abalone, as it often generates benign traits in the hybrids. The hybrids of Haliotis discus hannai and H. gigantea have shown heterosis in terms of disease resistance than one or both parental species. In the present study, to elucidate the physiological and molecular mechanism of this heterosis, we analyzed the dynamic changes of several immune indexes including survival rate, total circulating haemocyte count (THC), phagocytic activity, reactive oxygen species level (ROS) and phenoloxidase activity (PO) in two parental species, H. discus hannai (DD) and H. gigantea (GG), and their reciprocal hybrids H. discus hannai ♀ × H. gigantea ♂ (DG), H. gigantea ♀ × H. discus hannai ♂ (GD) challenged with a mixture of Vibrio harveyi, V. alginolyticus and V. parahaemolyticus (which have been demonstrated to be pathogenic to abalone). Besides, we cloned and analyzed three important immune genes: heat shock protein 70 (hsp70), ferritin and cold shock domain protein (csdp) in H. discus hannai and H. gigantea, then further investigated their mRNA level changes in the four abalone genotypes after bacterial challenge. Results showed that these physiological and molecular parameters were significantly induced by bacterial exposure, and their changing patterns were obviously different between the four genotypes: (1) Survival rates of the two hybrids were higher than both parental species after bacterial exposure; (2) DG had higher THC than the other three genotypes; (3) Phagocytosis responded slower in the hybrids than in the parental species; (4) DD's ROS level was lower than the other three genotypes at 48 h post infection; (5) Phenoloxidase activity was lower in DD during the infection compared to the other genotypes; (6) mRNA levels of hsp70 and csdp, were always lower in at least one parental species (DD) than in the hybrids after the bacterial exposure. Results from this study indicate that the hybrids are more active or efficient in immune system function, hence they could effectively defense against a bacterial invasion, leading to higher survival rates after challenge. This study provides physiological and molecular evidences for interpreting the disease resistant heterosis in this abalone hybrid system, which could help us in a better understanding and utilization of heterosis in abalone aquaculture.

Differences in innate and adaptive immune response traits of Pahari (Indian non-descript indigenous breed) and Jersey crossbred cattle.

Cattle are an integral part of the largely agrarian economy of India. Indigenous breeds of cattle comprise about 80% of total cattle population of the country and contribute significantly to the overall milk production. There are 40 recognized indigenous breeds of cattle and a number of uncharacterized non-descript cattle. Pahari cattle of Himachal Pradesh in Northern India are one such non-descript indigenous breed. Here we describe a comprehensive evaluation of haematobiochemical parameters and innate and adaptive immune response traits of Pahari cattle and a comparison with Jersey crossbred cattle. The study shows demonstrable differences in the two breeds with respect to some innate and adaptive immunological traits. This is a first attempt to characterize immune response traits of Pahari cattle and the results of the study provide an understanding of breed differences in immune status of cattle which could be useful for their breeding and conservations programs.

Mycoplasma pneumonia of swine (MPS) resistance and immune characteristics of pig lines generated by crossing an MPS pulmonary lesion selected Landrace line and a highly immune capacity selected Large White line.

To understand the influence of crossbreeding on Mycoplasma pneumonia of swine (MPS) resistance and immune characteristics, two crossbred lines were characterized. One crossbred line, LaWa, was generated by crossing the MPS pulmonary lesion selected Landrace line (La) and the highly immune-selected Large White line (Wa). The second crossbred line, LaWb, was generated by crossing the La line and the nonselected Large White line (Wb). The crossbred LbWb line (nonselected Landrace line × nonselected Large White line) and the La line were used as controls. The LaWa and LaWb lines had an intermediate level of MPS lung lesions between La and LbWb lines, although the difference was not statistically significant. After stimulation with sheep red blood cells (SRBCs), the LaWb and LaWa lines showed immune characteristics similar to that of the La line; the number of monocytes in peripheral blood increased, while B cells, T cells, secretion of SRBC-specific immunoglobulin G, and interleukin (IL)-13 decreased. Additionally, the number of natural killer (NK) cells and the expression of IL-4 and IL-17 were significantly higher in the LaWb and LaWa lines, respectively. These data suggested that crossbreeding of La and Wa lines resulted in the inheritance of some of the selected immune responses.

The role of hybridization in improving the immune response and thermal tolerance of abalone.

Recently, frequent death of cultured abalone drew our attention to the stress tolerance of abalone. Hybridization is an effective way of genetic improvement in aquaculture, which can introduce improved traits to the hybrids. In this study, we challenged the hybrids between Haliotis discus hannai and Haliotis gigantea, and their parents with bacteria (vibrio harveyi, vibrio alginolyticus and vibrio parahemolyticus), then held them at 20 °C and 28 °C, survival rates of the parental populations and hybrid populations were recorded. Then we tested the immune responses and thermal-induced responses of the four populations at different temperatures. Total hemocyte count (THC), respiratory burst, superoxide dismutase activity (SOD), acid phosphatase activity (ACP), alkaline phosphatase activity (AKP), myeloperoxidase activity (MPO), and HSP70 expression were determined on day 1 and day 7 of the temperature exposure. Results showed higher survival rates of the hybrids than their parents against bacteria challenge. For immune parameters, THCs were evaluated at 28 °C, while increased THC was also observed in H. discus hannai ♀ × H. gigantea ♂ (DG) and H. discus hannai ♀ × H. discus hannai ♂ (DD) at 12 °C (day 7); at 28 °C, respiratory burst was activated (day 1 and 7), while SOD activity first rose then fell over 7-days exposure; AKP activity was elevated at 12 °C and 28 °C (day 1), most notably in DG, and an increased level of ACP was observed in DG at 28 °C (day 7); MPO activity was suppressed at 12 °C and 28 °C on day 1, but recovered on day 7. For HSP70, increased HSP70 levels were observed in all populations at 28 °C (day 1), and DD got the lowest HSP70 level after 7-days exposure at 28 °C. Overall, the results suggest that temperature changes could significantly affect the physiological status of abalone, and hybrids may be more resistant to disease and thermal stresses than their parents.

Bighorn sheep × domestic sheep hybrids survive Mannheimia haemolytica challenge in the absence of vaccination.

Bighorn sheep (BHS, Ovis canadensis) are much more susceptible than domestic sheep (DS, Ovis aries) to pneumonia caused by leukotoxin (Lkt)-producing members of the Family Pasteurellaceae, particularly Mannheimia haemolytica and Bibersteinia trehalosi. Leukotoxin is widely accepted as the critical virulence factor of these bacteria since Lkt-negative mutants do not cause death of BHS. Typically, DS carry Lkt-positive M. haemolytica and/or B. trehalosi as commensal bacteria in their nasopharynx. In contrast, most BHS do not carry Lkt-positive M. haemolytica or B. trehalosi, or carry Lkt-negative strains in their nasopharynx. In previous studies, we demonstrated that unimmunized DS resist M. haemolytica challenge while BHS succumb to it. We hypothesized that Lkt-neutralizing antibodies, induced by Lkt-positive M. haemolytica and/or B. trehalosi innately carried by DS in their nasopharynx, render them less susceptible to infection by these bacteria. In this study we developed BHS×DS F1 hybrids by artificial insemination of domestic ewes with BHS semen. F1 hybrids were fertile, and produced F2 hybrids and back-crosses. The F1, F2, and back-crosses were raised together with domestic ewes. All these animals acquired Lkt-positive M. haemolytica and/or B. trehalosi, and developed high titers of Lkt-neutralizing antibodies in the absence of vaccination. Furthermore, all of these animals resisted challenge with lethal dose of M. haemolytica. These results suggest that lack of previous exposure to Lkt is at least partially responsible for fatal pneumonia in BHS when they acquire Lkt-positive M. haemolytica and/or B. trehalosi from DS when the two species commingle.

The expression of IL6 and 21 in crossbred calves upregulated by inactivated trivalent FMD vaccine.

Foot and mouth disease (FMD) is an economically important disease and a whole-virus inactivated trivalent virus vaccine is the mainstay for controlling the disease in India. The protective humoral immune response to FMD vaccination is a complex, but, tightly regulated process mediated by the interplay of interleukins (IL). Based on the specific role of IL6 and 21 in adaptive immune response, we hypothesized that inactivated trivalent FMD vaccine would stimulate IL6 and 21 expression in the circulating lymphocytes. The expressions of IL6 and 21 were assayed on 0, 28, 60, 90, and 120 d post-vaccination (DPV) by quantitative PCR (qPCR) with simultaneous assessment of FMDV antibody titer by liquid phase blocking ELISA. The results revealed that the peak expression of IL6 and 21 was on DPV 28 which correlated well with the FMDV antibody titer and plummeted to the prevaccination titer level by 60 DPV. As IL21 is the final effector of antibody production as compared to IL6, we investigated the expression of IL21 in calves that had protective titer (>1.8) with the unprotected group (<1.8). Expression of IL21 on 28 DPV was numerically higher in the protected than that of the unprotected group of calves.

Effect of Lactobacillus plantarum C014 on innate immune response and disease resistance against Aeromonas hydrophila in hybrid catfish.

A bacterial strain isolated from intestines of hybrid catfish (Clarias gariepinus Male × Clarias macrocephalus Female) exhibited an in vitro inhibitory effect on a fish pathogen, Aeromonas hydrophila TISTR 1321. By using the 16S rDNA sequence analysis, it was identified as Lactobacillus plantarum C014. To examine whether L. plantarum C014 had potential for use as an immunostimulant and biocontrol agent in hybrid catfish, the fish diet supplemented with L. plantarum C014 (10(7) CFU/g diet) was prepared and used for the in vivo investigation of its effect on innate immune response and disease resistance of hybrid catfish. Two innate immune response parameters, phagocytic activity of blood leukocytes and plasma lysozyme activity, were significantly enhanced in the treated fish after 45 days of feeding. Feeding the fish with the L. plantarum C014 supplemented diet for 45 days before challenging them with A. hydrophila at the dose of LD50 could reduce the mortality rate of the fish from 50% (in control group) to 0% (in treated group). Based on its origin and beneficial effect on innate immune response and disease resistance, L. plantarum C014 may be a potential candidate for use as a natural and safe immunostimulant and biocontrol agent in hybrid catfish.

Impact of mouse pregnancy on thymic T lymphocyte subsets.

It has been reported that fetal lymphoid progenitor cells are acquired during gestation and are able to develop in the maternal mouse thymus into functional T cells. Moreover, previous pregnancies increase the number of fetal cells in the mother. In the present study, we investigated whether mouse pregnancy induces changes in T lymphocyte subsets in the maternal thymus. We determined the T lymphocyte subsets in two allogeneic cross-breedings, namely CBA/J×BALB/c (normal) and CBA/J×DBA/2 (abortion prone), and investigated the effects of the age and parity of the female, as well as pregnancy outcome, on thymocyte populations. In addition, hormonal effects were evaluated in a syngeneic combination (CBA/J×CBA/J). We found that during pregnancy both hormonal and allogeneic stimuli induced a reduction in the CD4(+)CD8(+) subset with an increase in the CD4(+)CD8(-) population. Only young females of the normal combination exhibited an increase in the CD4(-)CD8(+) population. All young mice showed an increase in CD4(+)CD25(+)FoxP3(+) T cells. Interestingly, the γδT thymus pool was increased in all females of the normal allogeneic pregnancy only, suggesting the participation of this pool in the observed beneficial effect of multiparity in this cross-breeding. Our results demonstrate that allogeneic pregnancies induce important variations in maternal thymocyte subpopulations depending on the age of the female and the male component of the cross-breeding.

Quantitative trait loci associated with the immune response to a bovine respiratory syncytial virus vaccine.

Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL) on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected.Heifers from the same population (n = 195) were subsequently immunised with a 40-mer Foot-and-Mouth Disease Virus peptide (FMDV) in a previous publication. Several of these QTL associated with the FMDV traits had overlapping peak positions with QTL in the current study, including the QTL on BTA23 which included the bovine Major Histocompatibility Complex (BoLA), and QTL on BTA9 and BTA24, suggesting that the genes underlying these QTL may control responses to multiple antigens. These results lay the groundwork for future investigations to identify the genes underlying the variation in clearance of maternal antibody and response to vaccination.

Antibody and cell-mediated immune responses and survival between Holstein and Norwegian Red × Holstein Canadian calves.

As an extension of a former study, the objectives of this study were to evaluate purebred Holstein (HO; n=140) and crossbred Norwegian Red × Holstein (NRFX; n=142) calves for antibody (AMIR) and cell-mediated immune responses (CMIR) as well as survival. Blood was collected on d 0, 14, and 21, and calves were immunized on d 0 and 14 with type 1 (Candida albicans) and type 2 (hen egg white lysozyme) antigens, which have been shown to induce CMIR and AMIR, respectively. Day 21 background skin-fold measurements of either side of the tail-fold were taken and intradermal injections of test (type 1 antigen) and control (phosphate saline buffer) were administered. Day 23 final skin-fold measurements were taken to assess delayed type hypersensitivity as an indicator of CMIR. Survival data were obtained from CanWest Dairy Herd Improvement. Statistical Analysis System general linear models were used to analyze all immune response and survival data and to determine statistical significance between breeds. Results showed that NRFX had greater primary IgM, IgG, IgG1, and secondary IgG1 antibody response, as well as greater primary IgG1:IgG2 ratio to the type 2 antigen compared with HO. The NRFX also had greater primary IgG1 and IgG2, and secondary IgG2 antibody response as well as greater primary IgG1:IgG2 ratio to the type 1 antigen. The NRFX calves had a tendency toward greater survival from age at immune response testing to calving. No difference was observed between breeds for other secondary antibody response traits or delayed type hypersensitivity. Results indicate NRFX have greater AMIR and therefore may have enhanced defense against extracellular pathogens. This may contribute to increased survival compared with HO. Both breeds, however, likely have similar defense against intracellular pathogens, because no differences in CMIR were observed. In general, these results may suggest that crossbreeding could improve resistance to certain diseases in dairy calves, resulting in decreased input costs to producers for crossbred calves compared with purebred calves. However, more research with larger sample sizes and different breeds should be conducted to confirm these results and obtain a complete picture of the benefits of crossbreeding on immune response traits in calves.

Immune responses of Holstein and Norwegian Red x Holstein calves on Canadian dairy farms.

The objective of this study was to compare the immune response of Holstein and Norwegian Red x Holstein calves on 13 commercial Canadian dairy farms. Data were collected on 135 calves, 68 Holstein and 67 Norwegian Red x Holstein calves aged between 2 and 6 mo. The calves were immunized with hen egg white lysozyme to induce antibody-mediated immune response. Candida albicans was used as an in vivo indicator of cell-mediated immune response, with delayed-type hypersensitivity used as the indicator. Antibody response to hen egg white lysozyme (IgG, IgG1, and IgG2) was measured by ELISA. Calves of both breed groups produced a significant primary and secondary antibody-mediated immune response, as well as a delayed-type hypersensitivity reaction. The Norwegian Red x Holstein produced a greater primary IgG antibody-mediated immune response (d 14, and d 14 minus d 0) when compared with the Holstein. No differences were observed between the breeds for secondary response or antihen egg white lysozyme isotype (IgG1 or IgG2) production or the ratio of IgG1:IgG2. There was no effect of breed on delayed-type hypersensitivity. Nonetheless, high and low immune responders could be identified in both breed groups, but with no difference in the proportion of high and low responders observed for either antibody-mediated immune response or cell-mediated immune response between breed groups.

Relative dominance of epitope-specific CD8+ T cell responses in an F1 hybrid mouse model of respiratory syncytial virus infection.

CD8+ cytotoxic T lymphocytes are key effectors of adaptive immunity for the control of virus infections. Epitope-specific responses are hierarchical and the rules for dominance are not well defined. Here we show that the H2-Kd-restricted RSV M2(82-90) (KdM2(82-90)) epitope dominates the H2-Db-restricted RSV M187-195 (DbM187-195) epitope and influences epitope-specific effector function in the acute and memory phases of the immune response to primary RSV infection in H-2b/d hybrid mice. The hybrid mouse model provides a system to define rules of epitope hierarchy and better understand how antigen presentation and epitope competition affect the phenotype of effector and memory T cells.

Placental invasiveness mediates the evolution of hybrid inviability in mammals.

A central question in evolutionary biology is why animal lineages differ strikingly in rates and patterns of the evolution of reproductive isolation. Here, we show that the maximum genetic distance at which interspecific mammalian pregnancies yield viable neonates is significantly greater in clades with invasive (hemochorial) placentation than in clades with noninvasive (epitheliochorial or endotheliochorial) placentation. Moreover, sister species with invasive placentation exhibit higher allopatry in their geographic ranges, suggesting that formerly separated populations in mammals with this placental type fuse more readily on recontact. These differences are apparently driven by the stronger downregulation of maternal immune responses under invasive placentation, where fetal antigens directly contact the maternal bloodstream. Our results suggest that placental invasiveness mediates a major component of reproductive isolation in mammals.

Hepatitis B virus infection profile in Central Brazilian hemodialysis population

A hepatite B tem sido uma grande ameaca aos pacientes de hemodialise. Para investigar o perfil da infeccao pelo virus da hepatite B (VHB) na populacao de hemodialise de Goiania - Brasil Central, 282 pacientes foram estudados. A prevalencia de marcadores do VHB (AgHBs, anti-HBc e anti-HBs) foi de 56,7 por cento (IC 95 por cento: 51,1 - 62,7) variando de 33,3 por cento a 77,7 por cento entre as unidades de dialise. O VHB-DNA foi detectado nas amostras AgHBs positivas em 67,6 por cento e 88,2 por cento, nas AgHBs e AgHBe em 91,3 por cento e 100 por cento, e nas AgHBe e anti-HBe e soro reativas em 18,2 por cento e 63,6 por cento por hibridizacao e PCR, respectivamente. O tempo de tratamento hemodialitico mostrou-se estatisticamente associado a soropositividade ao VHB. Somente 10 por cento dos pacientes relataram vacinacao para a hepatite B. Assim, uma prevalencia elevada para infeccao pelo VHB nesta populacao e o risco aumentado do tempo de tratamento hemodialitico sugerem a transmissao ambiental deste virus...

Depletion of natural killer cells from the graft reduces interferon-gamma levels and lipopolysaccharide-induced tumor necrosis factor-alpha release in F1 hybrid mice with acute graft-versus-host disease.

BACKGROUND: We wished to determine whether removal of NK1.1+ cells from the graft provides protection against acute graft-versus-host disease (GVHD) by obviating the Th1 immune response that underlies the development of this disease. METHODS: Graft-versus-host (GVH) reactions were induced in two groups of (C57BL/6 x DBA/2)F1 hybrid mice. The first received grafts harvested from polyinosinic:polycytidylic acid-stimulated, C57BL/6 donors and depleted in vitro of NK1.1+ cells. This treatment provides protection against GVHD-associated mortality and cachexia. The second received unmodified grafts. We compared interferon-gamma and interleukin-10 production as well as the levels of engraftment in these two groups. Lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) release was also compared since TNF-alpha levels in GVH mice following injection of a sublethal dose of endotoxin provide an index of macrophage priming by Th1 cytokines. RESULTS: Interferon-gamma production was absent in recipients of NK1.1-depleted grafts at the time when high levels were seen in recipients of unmodified grafts. Following lipopolysaccharide injection, high levels of TNF-alpha were observed in recipients of unmodified grafts, whereas negligible amounts were present in recipients of NK1.1-depleted grafts. The use of NK1.1-depleted grafts did not result in a reduced level of engraftment of CD4+ or CD8+ cells. CONCLUSIONS: These results suggest that NK1.1 depletion of the graft confers protection against mortality by interfering with an immunoregulatory mechanism that results in the development of a Th1 response in GVH mice, and does not result in abortion of the graft. Because macrophage priming is prevented, recipients are also protected from the exaggerated sensitivity to endotoxin seen in mice with acute GVHD.

Genetic relationship of Corynebacterium diphteriae strains isolated from diphteria case and carriers by restriction fragment length polymorphism of rRNA genes

No presente estudo, nos reportamos os resultados de uma analise, baseada na ribotipagem de cepas de C. diphtheriae intermedius isoladas de uma crianca de 9 anos com difteria e seus 5 contatos. Analise quantitativa por RFLP de rRNA foi usada para determinar a relacao destas 7 cepas de C.diphtheriae fornecendo dados de interesse epidemiologico...

The NK1.1 antigen in NK-mediated F1 antiparent killing in vitro.

NK cells in lethally irradiated F1(A x B) hybrid mice can reject parental A or B strain bone marrow cells, a phenomenon called "hybrid resistance." The recognition mechanism used by the NK cells remains unknown. Our laboratory has previously described an in vitro model for hybrid resistance, and we have used it here to test whether the NK surface marker, NK1.1, is involved in such recognition. We found that 1) an anti-NK1.1 mAb (PK136) inhibited F1 lymphokine-activated killer (LAK) antiparent lysis if the LAK expressed NK1.1. Other mAb, even a mAb such as 2B4 that recognizes the same LAK as PK136, did not produce inhibition. 2) The F(ab')2 fragment of PK136 also inhibited lysis. 3) F1 LAK generated from athymic nude mice were as effective antiparent killers as LAK from normal mice and were equally inhibitable by anti-NK1.1 mAb, strengthening the conclusion that killing is mediated by NK cells and not T cells. 4) As previously shown by others, addition of anti-NK1.1 mAb to a mixture of NK1.1+ LAK cells and NK-resistant FcR+ cells allowed lysis of the FcR+ cells via "redirected lysis," in which the anti-NK1.1 mAb binds to NK1.1 on the NK cells and FcR on the target cell. The ability of anti-NK1.1 mAb to inhibit direct lysis and enhance redirected lysis is most consistent with NK1.1 being a receptor involved in NK activation.

Effects of non-MHC background genes on the induction of CD4+ T cells that prevent rejection of a highly immunogenic tumor, FBL-3.

This study showed that non-MHC genes common to (DBA/2 H-2d) and (DBA/1 H-2q) gave rise to suppressor T (Ts) cells in the hybrid F1 mice between C57BL/6 (B6) strain in the anti-FBL-3 tumor responses. FBL-3, a Friend virus-induced tumor cell line of B6 mouse origin, is highly immunogenic as shown by findings that syngeneic and hybrid F1 mice with several other inbred strains rejected up to 3 x 10(7) tumors cell inoculated s.c. and generated potent CTL responses after mixed lymphocyte tumor cell culture. In contrast to these mice, (B6 x DBA/2) and (B6 x DBA/1)F1 mice did not reject the tumor as the tumor doses increased. Progressive tumor growth in these F1 mice was blocked by an i.p. injection of cyclophosphamide (250 mg/kg) on day 10, but not on day 5, after tumor cell inoculation. Anti-CD4 (GK1.5) mAb exerted similar therapeutic effects against tumor when given twice, between day 0 and 10, whereas the additional injection of anti-CD8 mAb enhanced the tumor growth in mice that otherwise rejected the tumor. Thus, in the response of (B6 x DBA/2)F1 mice to FBL-3 tumor cells, CD4+ Ts seemed to down-regulate the immunologically mediated regression of the tumor produced by CD8+ CTL. This was evidenced by limiting dilution culture analyses, which showed that the frequency of an FBL-3-specific CTL precursor in the (B6 x DBA/2)F1 mice that rejected the tumor with anti-CD4 mAb was approximately 7- to 9-fold higher than that in mice in which the tumor regressed spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

One explanation for F1 antiparent responses.

The phenomenon of hybrid resistance, in which F1 offspring reject parental grafts, remains a perplexing problem. Here, Tina Dalianis and Lars Ahrlund-Richter propose that one component of the F1 antiparent response results from competition between the two sets of parentally derived major histocompatibility complex (MHC) molecules for 'promiscuous' peptides. Lack of tolerance in the F1 animal results from insufficient presentation of these peptides on the MHC molecule that has lower affinity for the peptides.