Vaccination with cell immunoglobulin mucin-1 antibodies and inactivated influenza enhances vaccine-specific lymphocyte proliferation, interferon-gamma production and cross-strain reactivity.

Influenza virus causes a contagious and potentially serious infection of the upper respiratory tract. While neutralizing antibodies are protective against infection, the problem of antigenic drift remains, requiring the constant monitoring and development of new vaccines. The magnitude of this situation is underscored by the emergence of new potentially human pathogenic influenza strains, avian H5N1 being the most recent example. We present evidence that antibodies against T cell immunoglobulin mucin-1 (TIM-1), a recently identified immunomodulatory molecule, stimulate cellular immunity against influenza viruses and cross-strain immune reactivity. To determine potential immunostimulatory properties of anti-TIM-1, mice were vaccinated with inactivated influenza virus in the presence or absence of TIM-1-specific monoclonal antibodies. Development of cellular immunity against both the influenza strain used for immunization and serotypically distinct virus strains was monitored 3 weeks after vaccination by determining antigen-specific lymphocyte proliferation and cytokine production. Results show that TIM-1 antibodies enhance antigen-specific cellular proliferation (P < 0.05) and interferon (IFN)-gamma production (P < 0.01). Using blocking anti-CD4 and CD8 antibodies, it was observed that antigen-specific cellular proliferation is CD4-dependent and that the majority of proliferating cells are CD4+. Finally, vaccination with inactivated influenza virus with TIM-1 antibody results in the significant (P < 0.001) induction of proliferation and IFN-gamma production upon stimulation with one of three serologically distinct strains. TIM-1 antibodies demonstrate an adjuvant effect promoting antigen-specific cellular proliferation and IFN-gamma production, which are important for the promotion of cell-mediated immunity. These results are the first to suggest that TIM-1 antibody may serve as a potent adjuvant in the development of new influenza virus vaccines.

Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity.

Natural killer (NK) cells attack many tumour cell lines, and are thought to have a critical role in anti-tumour immunity; however, the interaction between NK cells and tumour targets is poorly understood. The stimulatory lectin-like NKG2D receptor is expressed by NK cells, activated CD8+ T cells and by activated macrophages in mice. Several distinct cell-surface ligands that are related to class I major histocompatibility complex molecules have been identified, some of which are expressed at high levels by tumour cells but not by normal cells in adults. However, no direct evidence links the expression of these 'induced self' ligands with tumour cell rejection. Here we demonstrate that ectopic expression of the murine NKG2D ligands Rae1beta or H60 in several tumour cell lines results in potent rejection of the tumour cells by syngeneic mice. Rejection is mediated by NK cells and/or CD8+ T cells. The ligand-expressing tumour cells induce potent priming of cytotoxic T cells and sensitization of NK cells in vivo. Mice that are exposed to live or irradiated tumour cells expressing Rae1 or H60 are specifically immune to subsequent challenge with tumour cells that lack NKG2D ligands, suggesting application of the ligands in the design of tumour vaccines.

Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome.

Mice with a targeted disruption of the gene encoding a lymphoid-expressed orphan G protein-coupled receptor, G2A, demonstrate a normal pattern of T and B lineage differentiation through young adulthood. As G2A-deficient animals age, they develop secondary lymphoid organ enlargement associated with abnormal expansion of both T and B lymphocytes. Older G2A-deficient mice (>1 year) develop a slowly progressive wasting syndrome, characterized by lymphocytic infiltration into various tissues, glomerular immune complex deposition, and anti-nuclear autoantibodies. G2A-deficient T cells are hyperresponsive to TCR stimulation, exhibiting enhanced proliferation and a lower threshold for activation. Our findings demonstrate that G2A plays a critical role in controlling peripheral lymphocyte homeostasis and that its ablation results in the development of a novel, late-onset autoimmune syndrome.

Humoral and cell-mediated immunity in mice with genetic deficiencies of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormone.

Prolactin (PRL), growth hormone (GH), insulin-like growth factor-I (IGF-I), and thyroid hormones have been proposed as critical immunoregulatory mediators, and their clinical use is being considered. The precise role played by each of these hormones in the generation of humoral and cell-mediated immune responses was assessed in a panel of mice with mutations that result in a selective reduction of PRL, GH, IGF-I, and/or thyroid hormone production. A surprising result, in view of previous studies indicating an immunoregulatory role for these hormones, was that all mice generated normal humoral and cell-mediated immune responses following challenge with T-independent and T-dependent antigens and with Listeria monocytogenes. A review of these findings in the context of previous data has resulted in the formulation of a working hypothesis proposing that these hormones act as anabolic and/or stress modulating mediators with effects on most cells, including those of the immune system. When considered in this context, it is possible to reconcile the contradictory data.

Bilateral internal carotid artery dissection due to trivial trauma.

Internal carotid artery dissection (ICAD) is a known cause of unilateral headache and focal cerebral ischemic symptoms. Other symptoms include oculosympathetic paresis, facial pain, neck pain, subjective carotid bruits, and cranial nerve deficits. Traumatic dissection has an obvious precipitating incident preceding the neurologic or visual symptoms. An ICAD that occurs spontaneously or from trivial trauma usually lacks an obvious incident and thus requires awareness of its possibility for accurate detection and treatment. Dissections arise from a defect in the internal elastic lamina allowing penetration of blood into the arterial wall. Despite its low incidence, ICAD must be considered in young to middle-aged patients who present with headache and transient cerebral or retinal ischemic symptoms. This report describes a patient who had bilateral internal carotid artery dissections following trivial trauma. The etiologies, clinical manifestations, diagnostic modalities, treatment options, and outcomes of ICAD are discussed.

Staphylococcus aureus sortase mutants defective in the display of surface proteins and in the pathogenesis of animal infections.

Many gram-positive bacteria covalently tether their surface adhesins to the cell wall peptidoglycan. We find that surface proteins of Staphylococcus aureus are linked to the cell wall by sortase, an enzyme that cleaves polypeptides at a conserved LPXTG motif. S. aureus mutants lacking sortase fail to process and display surface proteins and are defective in the establishment of infections. Thus, the cell wall envelope of gram-positive bacteria represents a surface organelle responsible for interactions with the host environment during the pathogenesis of bacterial infections.

Fas (CD95)-dependent cell-mediated immunity to Listeria monocytogenes.

Two distinct and complementary pathways, one mediated by perforin and the other dependent upon CD95 (Fas), effect cell-mediated cytotoxicity. We examined the relative roles of these pathways in host defenses against the intracellular bacterial pathogen Listeria monocytogenes by using murine listeriosis as a model system. Mice which lacked both perforin and Fas (P0L0) were generated, and their responses to primary and secondary listeriosis were compared to those of wild-type (WT), Fas-deficient (L0), and perforin knockout (P0) mice. Relative to WT mice during primary listeriosis, P0 mice exhibited a reduced capacity to clear the infection from their spleens but not their livers whereas L0 mice had elevated bacterial titers in their livers and a modestly increased titer in their spleens. In contrast, bacterial titers in P0L0 mice were increased approximately 50- to 560-fold in their spleens and 230- to 1, 000-fold in their livers; eventual clearance of listeriae from both organs was significantly delayed. Furthermore, the resistance of P0L0 mice to secondary listeriosis was significantly reduced in their spleens and livers compared to that of WT, P0, or L0 mice. In vitro experiments indicated that immune cytotoxic T lymphocytes (CTL) lysed L. monocytogenes-infected hepatocytes primarily via a Fas-dependent, perforin-independent mechanism. The absence of Fas severely abrogated the lysis of infected hepatocytes by immune CD8(+) CTL. Taken together, these results provide the first evidence for Fas-dependent CTL-mediated lysis of L. monocytogenes-infected hepatocytes and demonstrate complementary roles for Fas and perforin in host defenses against an intracellular bacterial pathogen.

Recombinant Listeria monocytogenes vaccination eliminates papillomavirus-induced tumors and prevents papilloma formation from viral DNA.

Listeria monocytogenes is a gram-positive, facultative intracellular bacterium that enters the cytoplasm of infected cells and spreads directly into neighboring cells without encountering the extracellular environment. Cytoplasmic L. monocytogenes efficiently presents secreted proteins to the major histocompatibility complex class I pathway which can stimulate protective T-cell-mediated immune responses. We have used a cottontail rabbit papillomavirus (CRPV) rabbit model to test the ability of recombinant L. monocytogenes strains secreting the viral E1 protein (E1-rLm) to protect outbred rabbits against CRPV- and CRPV DNA-induced tumors. CRPV infection of outbred rabbits serves as a model for oncogenic papillomaviruses since CRPV-induced papillomas progress with high frequency to malignant carcinoma. Rabbits were vaccinated with wild-type L. monocytogenes or E1-rLm and then challenged with CRPV or viral DNA. In contrast to 0% papilloma regression in control animals, 77% of E1-rLm-vaccinated rabbits generated protective immunity that controlled and induced complete regression of tumors induced by CRPV. Latent viral DNA was not detected at 71% of the papilloma regression sites examined 4.5 months postregression. E1-rLm responder rabbits were completely resistant to papilloma formation from viral DNA. In contrast to controls, peripheral blood mononuclear cells from E1-rLm responder rabbits were able to proliferate in response to in vitro E1 stimulation. These results indicate that E1-rLm immunization generated a systemic anti-CRPV E1 cell-mediated immune response which protected outbred rabbits from tumors induced by CRPV or CRPV DNA challenge.

Recombinant Listeria monocytogenes as a live vaccine vehicle and a probe for studying cell-mediated immunity.

The ability of Listeria monocytogenes (L. monocytogenes) to enter the cytosol of host cells allows secreted proteins to efficiently enter the endogenous antigen-processing pathway leading to presentation by MHC class I molecules. L. monocytogenes has recently been exploited as a live vaccine vehicle for the induction of immunological memory against heterologous antigens. We have established a genetic system for site-specific integration of antigen expression cassettes into the Listeria genome which allows regulated expression and secretion of heterologous proteins. The ability of recombinant strains to stimulate long-term immunological memory and CD8+ T-cell-mediated protective immunity was investigated using the lymphocytic choriomeningitis virus (LCMV) murine infection model. Vaccination of mice with recombinant Listeria strains expressing LCMV antigens induced LCMV-specific CD8+ T cells which protected mice against LCMV challenge. We have also used a cottontail rabbit papillomavirus model to test the ability of recombinant Listeria strains to stimulate protective antitumor immunity in domestic rabbits. These studies have demonstrated the protective efficacy of recombinant L. monocytogenes vaccines and have established an experimental system for systematic analysis of cytotoxic T-cell induction by an intracellular bacterium.

Determinants of extramarital sex in the Philippines.

Understanding the factors associated with sexual behaviour is critical in slowing the spread of HIV in the Philippines, where sexual transmission accounts for most HIV infections, with the majority from heterosexual activity. Further, unprotected sex is common, as is sex with prostitutes. These factors increase the risks associated with extramarital sex. From an analysis of a nationally representative sample of women, we found that a number of factors were related to women's reports of their husbands' sexual activity outside their current relationship: women report that partners who are more educated, have been in the current relationship longer, and who had sex before marriage are more likely to be engaging in sex outside the marriage. Further, men who are older, who are farmers, who live at home, and who have more educated wives, were believed to be less likely to be having extramarital sex.

PIP: As of 1994, an estimated 15,000-50,000 people were infected with HIV in the Philippines. 95% of all known infections in the country were transmitted sexually, with 70% due to heterosexual intercourse. People commonly have unprotected sex and sex with prostitutes in the Philippines. Data on a nationally representative sample of women from the 1993 Philippines National Demographic Survey and the 1994 Philippines National Safe Motherhood Survey were analyzed to identify the factors associated with extramarital sexual behavior in the country. Women reported that husbands who are relatively more educated, have been in the current relationship longer, and who had sex before marriage are more likely to be having sex with someone other than their wives. Older men, farmers, men who live at home, and those with more educated wives were thought less likely to be having extramarital sex.

Major histocompatibility class I presentation of soluble antigen facilitated by Mycobacterium tuberculosis infection.

Cell-mediated immune responses are essential for protection against many intracellular pathogens. For Mycobacterium tuberculosis (MTB), protection requires the activity of T cells that recognize antigens presented in the context of both major histocompatibility complex (MHC) class II and I molecules. Since MHC class I presentation generally requires antigen to be localized to the cytoplasmic compartment of antigen-presenting cells, it remains unclear how pathogens that reside primarily within endocytic vesicles of infected macrophages, such as MTB, can elicit specific MHC class I-restricted T cells. A mechanism is described for virulent MTB that allows soluble antigens ordinarily unable to enter the cytoplasm, such as ovalbumin, to be presented through the MHC class I pathway to T cells. The mechanism is selective for MHC class I presentation, since MTB infection inhibited MHC class II presentation of ovalbumin. The MHC class I presentation requires the tubercle bacilli to be viable, and it is dependent upon the transporter associated with antigen processing (TAP), which translocates antigenic peptides from the cytoplasm into the endoplasmic reticulum. The process is mimicked by Listeria monocytogenes and soluble listeriolysin, a pore-forming hemolysin derived from it, suggesting that virulent MTB may have evolved a comparable mechanism that allows molecules in a vacuolar compartment to enter the cytoplasmic presentation pathway for the generation of protective MHC class I-restricted T cells.

Determinants of two major early-childhood diseases and their treatment in the Philippines: findings from the 1993 National Demographic Survey.

PIP: Data on infants and children aged under 5 from the 1993 National Demographic Survey of the Philippines were analyzed to determine the conditions under which infants and children become ill with an acute respiratory infection (ARI) or diarrhea and either receive or do not receive treatment. Overall, parental education, father's occupational status, and residence in Metro Manila had a negative association with current illness but a positive association with the quality of health care provided. Rates for ARI and diarrhea were higher in urban areas than rural areas. Mothers working in a professional position tended not to bring their child ill with ARI for treatment. Women who did not use the mass media very often did moderately better on both the morbidity and treatment indicators than their counterparts. Filipino Muslims rarely took any child ill with ARI to a health care provider. They knew less about oral rehydration therapy (ORT) and used ORT less than other groups. Work status of the mother, single-parenthood status, and sex of child were minor determinants of disease or treatment. Unwanted children and children born after short birth intervals tended to fare poorly. Age of child and the severity of the child's symptoms were generally associated with the morbidity and treatment factors. Low levels of morbidity occurred in infancy and around age 5. Morbidity peaked at about 18 months old. These findings indicate that lower socioeconomic status couples accept ORT and community health stations more than wealthier and better educated couples.^ieng

Antiviral cytotoxic T-cell memory by vaccination with recombinant Listeria monocytogenes.

Listeria monocytogenes is a facultative intracellular bacterium that is able to escape phagocytic vesicles and replicate in the cytoplasm of infected cells. As with viral vectors, this intracytoplasmic life cycle provides a means for introducing foreign proteins into the major histocompatibility complex class I pathway of antigen presentation. Using recombinant L. monocytogenes (rLM) strains expressing the full-length nucleoprotein (NP) or a single cytotoxic T-lymphocyte (CTL) epitope from lymphocytic choriomeningitis virus (LCMV), we analyzed antiviral CTL responses induced by rLM vaccination. After vaccination, rLM was cleared from the host within 7 days while inducing an LCMV-specific ex vivo CD8+ effector CTL response. Virus-specific CTL memory was maintained for 6 months postvaccination, as demonstrated by vigorous secondary CTL responses after in vitro stimulation. A single immunization with rLM that expressed either the full-length NP gene or the CTL epitope alone resulted in LCMV NP-specific CTL precursor frequencies of approximately 1/10(4) CD8+ T cells. A second rLM vaccination resulted in enhanced virus-specific CTL activity and in vitro proliferation. rLM-vaccinated mice were protected against chronic viral infection by an accelerated virus-specific memory CTL response. These mice cleared infectious virus as well as viral antigen, suggesting that sterilizing immunity was achieved. In contrast to mice that received wild-type LM, rLM-vaccinated mice were protected from virally induced immunosuppression and splenic atrophy associated with chronic LCMV infection. The ability to elicit long-term cell-mediated immunity is fundamental in designing vaccines against intracellular pathogens, and these results demonstrate the efficacy of recombinant LM vaccination for inducing protective antiviral CTL memory.

The fertility impact of alternative family planning distribution channels in Indonesia.

Clinic-based distribution of contraceptive commodities is expensive per unit distributed. This situation has fueled the search for alternative means of delivery. Comparing the performance of alternatives is straightforward if the output measure is a count of commodities distributed, but comparing actual fertility impacts is another matter. I use data from the 1991 Indonesia Demographic and Health Survey to assess the extent of difference among the eventual fertility outcomes of users supplied with similar commodities through varying sources. When the "modern" methods of pill, IUD, and injection are grouped together, the fertility of users supplied with these commodities differs markedly according to their source of supply. I find little evidence for self-selecting of users into supply channels. This result implies that fertility differentials by source are likely due to characteristics of the distribution channels.

Recombinant Listeria monocytogenes as a live vaccine vehicle for the induction of protective anti-viral cell-mediated immunity.

Listeria monocytogenes (LM) is a Gram-positive bacterium that is able to enter host cells, escape from the endocytic vesicle, multiply within the cytoplasm, and spread directly from cell to cell without encountering the extracellular milieu. The ability of LM to gain access to the host cell cytosol allows proteins secreted by the bacterium to efficiently enter the pathway for major histocompatibility complex class I antigen processing and presentation. We have established a genetic system for expression and secretion of foreign antigens by recombinant strains, based on stable site-specific integration of expression cassettes into the LM genome. The ability of LM recombinants to induce protective immunity against a heterologous pathogen was demonstrated with lymphocytic choriomeningitis virus (LCMV). LM strains expressing the entire LCMV nucleoprotein or an H-2Ld-restricted nucleoprotein epitope (aa 118-126) were constructed. Immunization of mice with LM vaccine strains conferred protection against challenge with virulent strains of LCMV that otherwise establish chronic infection in naive adult mice. In vivo depletion of CD8+ T cells from vaccinated mice abrogated their ability to clear viral infection, showing that protective anti-viral immunity was due to CD8+ T cells.

Contraceptive pricing and prevalence: family planning self-sufficiency in Indonesia.

Imposing or increasing user fees can move family planning programs toward self-sufficiency. But, economic theory predicts that quantities demanded decrease following price increases; and, that the size of the response depends, all else constant, upon the share of income accounted for by spending on the good or service. This article uses survey data collected in conjunction with an Indonesian self-sufficiency program to assess the differential magnitudes of contraceptive usage responses to price differentials between sample-wide and relatively poor households, and for both subsidized and full private-sector prices. We find a much more substantial response among poor households. As prices move up toward full cost-recovery, the effect is magnified.

Modulatory effects of plasma and serum on T lymphocyte activation: distinctive patterns for different mitogens.

Published reports have shown that fresh plasma, but not cryoprecipitate-depleted plasma or fresh serum, inhibits T cell activation by phytohemagglutinin (PHA). We sought to determine if this pattern of inhibition also characterized T cell responses to mitogens differing from PHA with regard to the cell surface molecules utilized for signal transduction. The activation system included colchicine, which limits the cells to one round of division, masking stimulatory factors that enhance proliferation by boosting the number of divisions per culture period. A distinctive modulatory pattern characterized T cell responses to each of 4 mitogens tested (PHA, anti-CD3 monoclonal antibody, desialyzed oxidized erythrocytes (DOE), pokeweed mitogen). Enhanced proliferative responses to anti-CD3 and DOE were observed in the presence of serum, and reflected an increased percentage of T cells expressing CD25. These findings suggest that concerns regarding a negative impact of plasma components on T cell responsiveness, when based on results from PHA-induced activations systems, may be unwarranted.

Lymphocyte subsets in HTLV-II-infected former blood donors: relationship to spontaneous lymphocyte proliferation.

Previous studies showed that over 70% of HTLV-seropositive blood donors from the Los Angeles area are infected with HTLV-II; further, mononuclear cells from about half of these HTLV-II+ donors exhibit spontaneous lymphocyte proliferation (SLP) during in vitro culture. To determine if HTLV-II+SLP+ donors exhibit more marked immune system changes than HTLV-II+SLP- donors, lymphocyte subsets for these two HTLV-II+ groups were compared to an uninfected control group. The percentage of lymphocytes expressing CD3 was significantly increased and the percentage expressing a CD16/56+CD3- phenotype (natural killer cells) was significantly decreased in the HTLV-II+SLP+ group (N = 34) versus the control group (N = 49). On the basis of absolute numbers, the lymphocyte number was significantly higher in the HTLV-II+SLP+ group than in the control group and reflected significant increases in the numbers of both CD4 and CD8 subsets of T cells. Analysis of proportional changes in CD4 and CD8 cell subsets revealed significant increases in the proportions of CD4 cells expressing HLA-DR, CD8 cells expressing HLA-DR, and CD8 cells expressing CD45RO for the HTLV-II+SLP+ group versus the control group. For all phenotypic parameters measured, no significant differences were noted when comparing the HTLV-II+SLP- group (N = 21) and the control group. Cell culture experiments utilizing purified CD4 cells and CD8 cells from a subset of each study group revealed that in vitro spontaneous proliferative capacity resides within both the CD4 cell and CD8 cell populations from SLP+ individuals. These findings show that changes in circulating lymphocyte subsets in HTLV-II infection are found only in association with SLP, and that the capacity to exhibit SLP characterizes both CD4 and CD8 lymphocyte subsets.

Phenotypic comparison of the three populations of human lymphocytes defined by CD45RO and CD45RA expression.

Published reports indicate that CD45RO-CD45RAbright T cells are native T cells, CD45RObrightCD45RA- T cells are memory T cells, and that concomitant loss of CD45RA expression and gain of CD45RO expression occurs during transition from naive to memory status. Thus, following in vitro activation of CD45RO- CD45RAbright T cells, a subset of transitional CD45ROdimCD45RAdim T cells is observed before conversion to a CD45RObrightCD45RA- phenotype is completed. Interestingly, all three of these phenotypic subsets are represented in the circulating human lymphocyte pool. We thus used dual-color flow cytometry to phenotypically characterize CD45RObrightCD45RA-, CD45ROdimCD45RAdim, and CD45RO- CD45RAbright lymphocytes. Both the CD45RObrightCD45RA- and CD45ROdimCD45RAdim subsets consisted almost entirely of T cells, whereas the CD45RO-CD45RAbright subset contained T cells plus essentially all of the B and natural killer cells. Additional studies used three-color flow cytometry to assess activation markers on T cells within the three subsets defined by CD45RO/CD45RA expression. CD25 expression increased with conversion from naive to memory status (5% of CD45RO-CD45RAbright, 24% of CD45ROdimCD45RAdim, and 42% of CD45RObrightCD45RA- T cells), whereas CD38 expression decreased during conversion (76, 53, and 27%, respectively). We also assessed the fluorescent intensities of CD11a, CD2, and CD44, shown by others to be increased on memory, compared to naive T cells. Visual inspection of fluorescence cytograms confirmed these findings, and further showed that transitional T cells express these markers at levels indistinguishable from those for naive T cells. These findings suggest that acquisition of CD25 and loss of CD38 occur relatively early in the naive-to-memory transition process, being evident in the transitional cell subset. In contrast, increased expression of CD11a, CD2, and CD44 appear to represent late events, occurring after loss of CD45RA and gain of CD45RO has been completed.

Culture-associated enhancement of LECAM-1 expression by lymphocytes and partial inhibition of enhancement by IL-4.

Recent studies have shown that the human leukocyte endothelial cell adhesion molecule-1 (LECAM-1) functions as a homing receptor, mediating leukocyte binding to high endothelial venules in peripheral lymph nodes. Increasing evidence has demonstrated that cytokines, such as IL-4, can modulate the expression of surface proteins such as homing receptors on a variety of cells. We thus investigated the modulatory effects of cytokines on LECAM-1 expression by lymphocytes using single- and dual-color flow cytometry. We found that the density of LECAM-1 expression increased markedly during 3 days of culture and that this culture-associated enhancement (CAE) of LECAM-1 expression was significantly inhibited by IL-4. B cells and both major T cell subsets (CD4, CD8) exhibited CAE of LECAM-1 expression, but the inhibitory effect of IL-4 on this response occurred only in the T cell populations. The inhibitory effect of IL-4 on enhanced LECAM-1 expression was reversible, and characterized all 3 LECAM-1 epitopes assessed. Natural killer cells, in contrast, did not exhibit CAE of LECAM-1 expression, and IL-4 had no modulatory effect on LECAM-1 expression by these cells. Another adhesion molecule, CD44, showed enhanced expression during culture, but this enhancement was not inhibited by IL-4. The results show that LECAM-1 expression by T and B lymphocytes is significantly increased during culture and that the inhibitory effect of IL-4 on this increase is restricted to T cells. These findings suggest that IL-4, generated during an immune response, may play a role in regulating the migration and localization of T lymphocytes to lymphoid tissues.