Uveitis in Blau syndrome from a de novo mutation of the NOD2/CARD15 gene.

Blau syndrome (MIM 186580) is a rare autoinflammatory, familial granulomatous condition that occurs secondary to a single amino acid mutation of the NOD2/CARD15 gene on chromosome 16p12-q21. We report the case of a 2.5-year-old girl who presented for ophthalmic examination in the setting of rash and synovitis. Initially, small, evanescent, ovoid corneal subepithelial opacities unique to Blau syndrome were observed. She later developed a fulminant panuveitis that responded to immunomodulatory therapy. Subsequent genetic testing confirmed the diagnosis of Blau syndrome. Despite immunosuppression, at almost 7 years of age, she continues to have persistent panuveitis with vision of 20/20.

Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Decreased bone strength in HLA-B27 transgenic rat model of spondyloarthropathy.

OBJECTIVE: To investigate the nature of osteopenia/osteoporosis in spondyloarthropathy, an inflammatory disorder, using the HLA-B27 transgenic rat model. METHODS: HLA-B27 transgenic rats were housed individually and sacrificed at the peak of their disease (8-month-old). The spine and femurs were removed and stored in saline at -20 degrees C until analysis. The bone structure and strength were determined using a micro-computed tomography (micro-CT) device (Scanco Medical) and mechanical testing (Instron 5543). Vertebral bodies and femurs were scanned to determine trabecular structural properties in terms of bone volume (BV/TV), trabecular thickness, and spacing. After scanning, the mid-shaft femurs were subjected to a 3-point bending test (along anterior-posterior direction), the femoral necks were tested in bending, and the vertebral bodies (L4) were tested in compression. Structural (ultimate/yield load, stiffness) and apparent material (ultimate/yield stress, modulus) strength parameters were then determined. RESULTS: The majority of the bone structural and strength parameters were significantly lower (P < 0.05) in the HLA-B27 transgenic rats as compared with control littermates. Micro-CT data suggested that the transgenic animals had lower BV/TV and trabecular thickness in their vertebral bodies. The poor trabecular structure observed in HLA-B27 rats is also indicative of the poor biomechanical strength properties in the vertebral bodies as well. CONCLUSION: The HLA-B27 transgenic rats develop bone fragility similar to that seen in spondyloarthropathy and may be an important model for the study of osteoporosis in spondyloarthropathy.

Cross-linking CD7 on myeloblasts results in granulocyte-macrophage colony-stimulating factor production.

CD7+CD34+ lymphohematopoietic progenitor cells in bone marrow are capable of differentiating into either lymphocytes or myeloid cells. The mechanism whereby these bipotent progenitor cells are regulated is not yet clear. In this study, we investigated the role CD7 may play in the development of bipotent cells using two myeloid progenitor cell lines, KG-1 and KG-1a, as models for such cells. Our data showed that cross-linking CD7 on KG-1 and KG-1a cells induced transcription, translation, and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). Anti-CD7 antibody also augmented the colony formation by KG-1 cells. Protein synthesis in KG-1 cells also increased as a result of anti-CD7 stimulation. These phenomena could be blocked by anti-GM-CSF, and supported the notion that the secreted GM-CSF was the primary mediator of CD7 effects. Together, these findings suggest that the interaction between CD7 and its putative ligand may play an important role in hematopoietic development.

Production and characterization of the extracellular domain of human CD7 antigen: further evidence that CD7 has a role in T cell signaling.

CD7 is a T cell-associated antigen which appears early in ontogeny and persists on circulating T cells. It appears to have a significant role in T cell development and function. The precise mechanism by which this molecule mediates its effect is not known. In this paper, we expressed the extracellular domain of CD7 in the baculovirus system and used this product to study the function CD7 might have in T cell activation. The recombinant protein was found to be structurally similar to the native CD7 and recognized by monoclonal and polyclonal antibodies to CD7. This protein inhibited T cell proliferation induced by anti-CD3/anti-CD7 costimulation. It also inhibited the augmentation effect of anti-CD7 on suboptimal PHA stimulation. However, it did not block T cell proliferation induced by optimal doses of PHA, staphylococcal entertoxin A or B. Interestingly, the recombinant protein inhibited antigenic- and alloantigenic-induced T cell proliferation. The latter finding strongly suggests that a ligand for CD7 exists and crosslinking CD7 by this ligand may be responsible for the costimulatory role it plays in T cell activation.

Augmentation of phorbol ester-induced T cell proliferation by agents which raise intracellular cyclic adenosine monophosphate.

Although raising intracellular cyclic adenosine monophosphate (cAMP) levels is generally considered to be inhibitory on the mitogen-induced T cell proliferation, in this study we have shown that the addition of either dbcAMP (50 microM) or cholera toxin (1 ng/ml) resulted in an increase in [3H]thymidine uptake in PBMC cultures stimulated with phorbol ester, 12-tetradecanoylphorbol 13-acetate (TPA), or with a combination of TPA plus anti-CD3 mAb (mAb 235). In contrast, under similar culture conditions, the phytohemagglutinin-P (PHA-P) response was inhibited by these agents as has been reported. The augmentative effect of dbcAMP in PBMC cultures was due to an increase in IL-2 production and not to increased in IL-2R-alpha chain expression. The enhancing effect of dbcAMP and CT observed with PBMC was monocyte dependent and not seen with purified T cell preparations. The addition of monocytes reconstituted the ability of intracellular cAMP elevating agents to augment the T cell response to TPA with and without mAb to CD3. The monocytes mediate their action via soluble factor(s) with molecular weight (m.w.) of more than 10 kDa. Neither rIL-1, rIL-6, nor rTNF-alpha have any augmentative effect as contrast with the supernatant from treated monocytes. Taken together, our results indicate that cAMP can play a positive regulatory role in T cell proliferation due to factor(s) secreted by dbcAMP-treated monocytes resulting in increased IL-2 synthesis in T cells.

CD7 augments T cell proliferation via the interleukin-2 autocrine pathway.

The role of CD7, a T cell differentiation antigen, in T cell function is not known at present; this study evaluates the effect of anti-CD7 mAb in PMBC cultures activated with suboptimal concentrations of lectins, antigens, and anti-CD3 mAb. We found that the inclusion of anti-CD7 resulted in increased IL-2 production and IL-2R-alpha expression in these cultures. H-7, a protein kinase C (PKC) inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor, significantly suppressed the proliferation of T cells in comitogenic assays. This suggested that the comitogenic effect mediated by CD7 molecule involved both the PKC and the PTK pathways of T cell activation. These drugs appeared to affect the CD7-mediated effects by inhibiting the IL-2 autocrine pathway, especially the up-regulation of IL-2R-alpha since inhibition was not relieved with exogenous rIL-2. Taken together, our results suggest that CD7 augments T cell function by up-regulating IL-2R-alpha expression and IL-2 production via multiple pathways of protein phosphorylation.

Association of aberrant F-actin formation with defective leukocyte chemotaxis and recurrent pyoderma.

A young boy with recurrent skin infections and slow wound healing was shown to have an isolated leukocyte chemotactic defect. The chemotactic abnormality was persistent throughout the observation period, could be demonstrated both in vivo and in vitro, and was not related to known causes of chemotactic defects. To investigate the underlying pathogenetic mechanism for this abnormality, the patient's polymorphonuclear (PMN) leukocytes were studied for their ability to respond to the chemotactic peptide N-formyl-methionylleucylphenylalanine (FMLP). The patient's leukocytes were able to bind FMLP normally and responded appropriately to the stimulus as shown by a rise in intracellular calcium after binding. However, his PMN leukocytes demonstrated abnormalities in the formation and disassembly of filamentous actin (F-actin), an important structural component in cell locomotion. Since the formation and disassembly of F-actin are important in the recycling of actin and crucial in the cell movement, the observed abnormalities may account for the disorder of chemotaxis seen in this patient. The findings in this case resemble the syndrome of neutrophil actin dysfunction. However, observed differences, including a much milder clinical disease, distinguish between these two clinical entities.

Expression of early activation antigen (CD69) during human thymic development.

The novel early activation antigen, EA1, has been shown to be induced by mitogens, antigens and the tumour promoter, phorbol myristate acetate (PMA), on human lymphocytes. This antigen has been designated to be CD69. EA1 has also been shown to be expressed on thymocytes without exogenous activation stimuli. In order to characterize further the expression of EA1 on thymocytes, the ontogeny of its expression was studied. EA1 appeared between 7 and 9.5 weeks of gestation, after colonization of the thymic rudiment with CD7+ T cell precursors, but before the onset of compartmentalization of the thymus into cortical and medullary zones. After cortico-medullary differentiation, the majority of medullary thymocytes expressed EA1 while only a fraction of the cortical thymocytes expressed this antigen. In the fetal and post-natal cortex, EA1 expression appeared to cluster in the subcapsular cortex. EA1+ cells were also scattered throughout the inner cortex. By two-colour fluorocytometric analysis of post-natal thymocytes, it was shown that EA1 was expressed on 30 to 65% of thymocytes. EA1 was expressed on CD4+ CD8+ as well as on the more immature CD4- CD8- thymocytes. In contrast to circulating T cells, thymocytes were much less responsive to PMA stimulation for the expression of EA1. Molecular characterization showed that EA1 on thymocytes had the same structure as that of activated peripheral T cells. In addition, thymic EA1 was constitutively phosphorylated. Thus, EA1 expression is acquired early during thymic development after colonization of the thymic rudiment by CD7+ T cell precursors. However, the specific role that EA1 may play in the activation and function of developing thymocytes remains to be determined.

Production of lymphotoxin by isolated human tonsillar B lymphocytes and B lymphocyte cell lines.

The expression of lymphotoxin (LT) mRNA and cytokine in human tonsillar B cells and B cell lines was examined by Northern blots and cytotoxicity assays, respectively. In tonsillar B cells, phorbol myristate acetate (PMA) or Staphylococcus aureus Cowan l (SAC) alone induced low levels of LT mRNA accumulation. However, SAC and anti-mu were strongly synergistic with PMA in this induction. Peak LT mRNA expression in tonsillar B cells stimulated by PMA plus SAC occurred between 48 and 72 h and was approximately half as much as that in PMA plus anti-CD3-stimulated T cells. Cyclosporine A was not effective in inhibiting LT mRNA accumulation by stimulated tonsillar B cells. A number of B cell lines could also be stimulated by PMA to express LT mRNA. Peak accumulation of LT mRNA in the cell line RPMI 1788 stimulated with PMA peaked about 8 h. A23187 in combination with PMA caused this accumulation to increase slightly and to peak earlier. The cytotoxic effects in the supernatants of stimulated B cells were contributed mostly by LT. The results indicate that tonsillar B cells are important in LT production and that there are important differences in the stimulation requirements for LT production and in LT mRNA expression kinetics between tonsillar B cells and B cell lines.

A sandwich CD7-ELISA for detection of solubilized CD7 from normal and leukemic T cells.

CD7 is a T differentiation antigen which is useful in the identification of precursor T cells as well as an important marker for the identification of leukemic T cells. It has proved to be useful as a target for immunotherapy by immunotoxins in several clinical settings. Most monoclonal antibodies to this antigen bind to the same or similar epitope. We have produced a monoclonal antibody, 69, which identifies a different epitope as that of the prototypic mAb to CD7, 3A1. Using mAB 69, we have devised a sandwich CD7-ELISA to detect solubilized CD7 antigen, with mAb 69 in the solid phase as the capturing mAb. This assay is sensitive and is able to detect antigen present on 2-5 x 10(4) activated T cells. This assay has been used to study the fate of CD7 on the membrane and in the cytosol of T cells during the process of mitogenesis. We have also utilized this assay to demonstrate the presence of free CD7 antigen in culture supernatant of activated T cells. This method will be useful to analyze antigen recovery from bulk cell cultures or from molecularly engineered microbial organisms. In addition, the sandwich CD7-ELISA may prove useful in monitoring the effects of immunotherapy in patients with leukemia.

Dissociation of TPA-induced down-regulation of T cell antigens from protein kinase C activation.

The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) has diverse effects on lymphoid cell function. Two of the early effects were the induction of early activation antigen EA1 and the down-regulation of certain T cell differentiation antigens (CD3, CD4, CD7). The mechanisms of these TPA effects were investigated. It was confirmed that EA1 expression was dependent on protein kinase C (PKC) activation. Synthetic diacylglycerols were capable of inducing EA1 expression. In addition, inhibition of PKC by the kinase inhibitor, H7, led to the inhibition of EA1 expression induced by TPA and synthetic diacylglycerols. In contrast, down-regulation of T cell differentiation antigens by TPA was not dependent on PKC activation. Synthetic diacylglycerols did not induce down-regulation of T cell antigens and H7 had no effect on the down-regulation of T cell antigens induced by TPA. These data would suggest that TPA exerted its effects on T cell function by mechanisms in addition to the activation of PKC alone. One possible mechanism would be the activation of the calmodulin-dependent pathway(s) since its inhibition resulted in the reversal of TPA-induced down-regulation of the T cell differentiation antigens.

The 28-kDa/32-kDa activation antigen EA 1. Further characterization and signal requirements for its expression.

The tumor promoter PMA has been shown to induce the expression of a 28-kDa/32-kDa early activation Ag, termed EA 1, on resting T cells. Under nonreducing conditions, EA 1 was detected by SDS-PAGE as a diffuse band in the 60-kDa region. In this study, this diffuse band was resolved into 56-kDa and 60-kDa bands. Endoglycosidase F treatment of EA 1 resulted in the appearance of a single band with a Mr of 48 kDa. Upon reduction, the 48-kDa band was shown to be composed of 24-kDa peptides. Diagonal gel electrophoresis showed that the major band of EA 1 was composed of a series of disulfide-linked homodimers with subunits of the same 24-kDa core protein that were differentially glycosylated. This analysis also revealed in a minor population of the EA 1 molecules, the presence of proteins of different Mr associated with the core protein. The signal requirements for the induction of EA 1 were investigated. The putative cellular action of PMA is the activation of protein kinase C (PKC). To further investigate the role of PKC activation in the expression of EA 1, the synthetic diacylglycerol, 1,2-sn-dioctanoylglycerol (diOG) was examined for its ability to substitute for PMA. DiOG induced EA 1 expression in a dose dependent manner. H-7, a relatively selective inhibitor of PKC, blocked diOG and PMA induced EA 1 expression. HA1004, a selective inhibitor of cAMP- and cGMP-dependent protein kinases, had no effect. In kinetic studies, EA 1 expression was seen as early as 1 h in diOG- and PMA-activated T cells. However, diOG did not completely mimic PMA-induced EA 1 expression. By 18 h, diOG-induced EA 1 expression was markedly reduced, whereas PMA-induced EA 1 expression was persistent. The role of calcium in EA 1 expression was investigated. mAb against CD3 potentiated diOG-induced EA 1 expression. This potentiation appeared to correlate with the ability of the anti-CD3 mAb to induce rises in intracellular calcium. Addition of EGTA to the media blocked the potentiation of diOG induced EA 1 expression by these mAb. The role of calcium in EA 1 expression was further demonstrated by the ability of ionomycin to potentiate EA 1 expression. These results demonstrate that PKC activation is the primary pathway for the induction of EA 1. However, calcium-dependent pathways appear to have a secondary role.

Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells.

The production of TNF/cachectin by human B cell lines and tonsillar B cells was examined. Of the 15 B cell lines examined, 9 cell lines synthesize TNF mRNA constitutively. PMA stimulated most cell lines to accumulate increased amounts of TNF. SeD, 8866P, 32al, RPMI 1788, and four bone marrow-derived EBV-transformed cell lines accumulated high levels of TNF mRNA when stimulated by PMA. TNF production by these cell lines was examined. RPMI 1788 and WIH8 produced little TNF constitutively, but synthesized 5-7 ng/ml TNF when stimulated by PMA. A pre-B cell line, Nalm-6, did not synthesize any detectable amount of TNF mRNA, even with PMA stimulation. Tonsillar B cells could also be stimulated to produce TNF. PMA or Staphylococcus aureus Cowan I strain (SAC) alone stimulated some TNF mRNA accumulation, whereas B cell growth factor (BCGF) or anti-mu did not. This accumulation was synergistically elevated by the combinations of PMA and SAC, or PMA and anti-mu. BCGF increased PMA-, SAC-, PMA plus SAC-, or PMA plus anti-mu-induced TNF mRNA accumulations about twofold. The accumulation of TNF mRNA in tonsillar B cells stimulated by PMA plus SAC was between 32 and 48 h, the same peak interval as the accumulation of TNF and IL-2 mRNA in tonsillar T cells. This is in contrast to PMA or PMA plus A23187-stimulated RPMI 1788 cells in which TNF mRNA accumulation was maximal at 1-2 h. TNF activities found in tonsillar B cell supernatants correlated with the TNF mRNA levels in the cells. However, more TNF activity was found on the second-day than the third-day supernatants, indicating active TNF uptake by the B cells. Cyclosporin A (CsA) inhibited SAC and anti-mu responses in B cells in much the same way as the anti-CD3 responses in T cells. SAC-, PMA plus SAC-, and PMA plus anti-mu-stimulated, but not PMA-stimulated, increases in TNF mRNA accumulations in tonsillar B cells were inhibited by CsA. TNF production seems to increase in parallel with B cell proliferation, but the relationship of these two functions needs to be further examined.

Effect of tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate on CD 7 expression by T lineage cells.

Phorbol esters exert diverse effects on cellular activation and differentiation. CD 7, a differentiation antigen appearing early in T cell ontogeny, may be involved in the activation and differentiation processes. CD 7 was found to be rapidly down-regulated by 12-O-tetradecanoylphorbol 13-acetate (TPA) from mature T cell surface. The time course of CD 7 down-regulation was similar to that of other functionally important T cell antigens, CD 3 and CD 4. Within 2 h, TPA at 10 to 30 ng/ml induced a complete down-regulation of CD 7. Twenty-four hours later, the reappearance of CD 7 on TPA-treated cells was observed. This phenomenon was monocyte independent. In contrast, CD 7 expression on thymocytes was resistant to the effect of TPA. In addition, certain leukemic T cells were also resistant to TPA-induced CD 7 down-regulation. The mechanism underlying TPA-induced CD 7 down-regulation was investigated further. Synthetic diacylglycerol, sn-1,2-dioctanoylglycerol, which activates protein kinase C, did not induce down-regulation of CD 7 on mature T cells. Ionomycin, a calcium ionophore, did not down-regulate this antigen either. Thus, it is concluded that the processes of protein kinase C activation and/or cytosolic calcium influx are not sufficient for TPA-induced CD 7 down-regulation; other pathways induced by TPA may be responsible.

Expression of a 33-kDa antigen Tm 1 on lymphocyte surface after modulation of cell surface antigens by IgM monoclonal antibody.

The mAb Tm 1 was obtained from a fusion of SP2/O tumor cells with spleen cells from CF1 mouse immunized with T cells modulated by an IgM anti-CD3 mAb.mAb Tm 1 reacted with IgM anti-CD3 modulated T cells (66.6%) but not with unmodulated T cells (4.4%). Tm 1 was not expressed on T cells modulated with either IgG2a or IgG1 anti-CD3 mAb. Immunoprecipitation from 125I-labeled CD3-modulated T cells showed that Tm 1 Ag is a single polypeptide of 33 kDa under reducing and nonreducing conditions. Kinetic studies revealed that Tm 1 was detectable on T cells 10 min after incubation and maximally expressed after 4 h of incubation with IgM anti-CD3 mAb. CD3 expression was markedly modulated by this anti-CD3 mAb after the same period of incubation. Studies with cycloheximide revealed that Tm 1 expression on T cells does not require new protein synthesis. Tm 1 expression persisted long after CD3-reexpression 24 h later. Tm 1 was present on a small fraction of circulating T cells, B cells, and monocytes and absent from granulocytes, platelets, E, and thymocytes. Tm 1 was not expressed on T cells after various activation stimuli but was expressed on B cells upon activation. Additional studies indicate that IgM mAb against other T cell differentiation Ag and IgM mAb against B cell Ag also lead to the expression of Tm 1 on these cells. Thus, modulation of surface Ag by IgM mAb externalizes this cytoplasmic Ag. However, one exception has been noted. Purified mAb Tm 1 was not mitogenic and was unable to block either the T cell proliferation induced by 12-O-tetradecanoyl phorbol-13-acetate plus anti-CD3 mAb and other T cell stimuli, or the B cell proliferation induced by B cell mitogens. The role of Tm 1 on lymphocyte function remains to be determined.

Human T cell activation. III. Rapid induction of a phosphorylated 28 kD/32 kD disulfide-linked early activation antigen (EA 1) by 12-o-tetradecanoyl phorbol-13-acetate, mitogens, and antigens.

With human T cells activated by 12-o-tetradecanoyl phorbol-13-acetate (TPA) as immunogen, an IgG2a mAb, early activation antigen 1 (EA 1), was generated against a 60-kD protein with disulfide-linked 28-kD and 32-kD subunits. Both subunits were phosphorylated. The antigen, EA 1, was readily detected on approximately 60% of isolated and cryopreserved thymocytes, as determined by indirect immunofluorescence. A low level of EA 1 expression was detectable on 6-7% of blood lymphocytes. TPA-activated T cells expressed EA 1 as early as 30 min after activation. By 1 h, 85-90% of the T cells stained with mAb EA 1. By 3-4 h, the expression of EA 1 was detected in greater than 95% of the T cells. Although the percentages of EA 1+ T cells did not change, the intensity of staining increased slightly. After 18-24 h, both the percentage of EA 1+ cells and the intensity of staining decreased gradually. TPA-induced EA 1 expression was independent of monocytes. EA 1 expression was slightly delayed in T cells that were isolated without the rosette selection and treated with TPA. Nevertheless, greater than 85% of these T cells expressed EA 1 within 1 h, and the maximal number of EA 1+ T cells was also detected at 3-4 h. In T cell populations with 1-2% monocytes, about 50-90% of the PHA- or Con A-activated T cells expressed EA 1 with a slower kinetics. EA 1 expression preceded that of IL-2-R in these activation processes. Similarly, T cells activated by soluble antigens (tetanus toxoid and PPD) and alloantigens in MLR also expressed EA 1 after a longer incubation. Approximately 20% of the T cells stained for EA 1 at day 6. EA 1 expression was not limited to activated T cells. B cells activated by TPA or anti-IgM antibody plus B cell growth factor expressed EA 1. The kinetics of EA 1 expression was markedly slower and the staining was less intense. Repeated attempts to detect EA 1 on resting and TPA-activated monocytes and granulocytes have not been successful. However, the detection of EA 1 in nonlymphoid cell lines would indicate that EA 1 may have a broader cell distribution. EA 1 expression was due to de novo synthesis, as the induction of EA 1 was blocked by cycloheximide and actinomycin D.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies on lymphocyte homing in autoimmune prone NZB mice.

Lymphocyte homing patterns in young (3-5 months old) and old (10-12 months old) autoimmune prone NZB mice were investigated by transferring 51Cr labelled lymphoid cells into syngeneic and H-2 compatible allogeneic recipients. We confirmed that non H-2 alloantigens as well as H-2 alloantigens can be important determinants of apparent abnormalities of cellular distribution with the techniques employed. No gross abnormalities of lymphocyte traffic were present in the young NZB mice as compared to the autoimmune resistant strains of mice when syngeneic cells are used. Spleen of older NZB mice appeared to be less attractive to lymph node cells than was the spleen from young NZB mice. Splenocytes of older NZB mice localized significantly more in the liver and less in the lymph nodes as compared with splenocytes from young NZB mice. The mechanism underlying abnormalities of lymphoid cell distribution which feature the autoimmune-prone NZB mice are not yet clear and further studies will be necessary before they can be characterized definitively. Our findings, using syngeneic cells, are in disagreement with those of Zatz and Lance since evidence of abnormal distribution of lymphocytes in young NZB mice were not seen when syngeneic cells were employed.