CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3.
Injection of anti-CD3 antibodies causes prompt expression of interleukin (IL)-4, IL-2, and interferon gamma (IFN-gamma) mRNA among spleen cells. The optimal dose of anti-CD3 for such induction was 1.33 microgram/animal; lymphokine mRNA was first observed at 30 min, peaked at 90 min, and was undetectable (for IL-4) or had declined markedly by 4 h. Cells harvested from spleens of mice injected with anti-CD3 90 min earlier secreted IL-4, IL-2, and IFN-gamma without further stimulation. By contrast, in vitro stimulation with anti-CD3 of spleen cell suspensions or splenic fragments from noninjected donors failed to cause prompt production of IL-4 and, even after 24 h of stimulation, the amount of IL-4 produced in such cells was substantially less than that secreted within 1 h by spleen cell suspensions or splenic fragments from mice injected with anti-CD3 90 min earlier. Production of IL-4 by spleen cells from anti-CD3-injected mice was not inhibited by pretreatment with anti-IL-4 antibody or with IFN-gamma or tumor growth factor beta nor enhanced by treatment with IL-4. By contrast, CTLA-4 immunoglobulin (Ig) treatment clearly diminished IL-4 production in response to in vivo anti-CD3, indicating that cellular interactions involving CD28 (or related molecules) were important in stimulation. Cell sorting analysis indicated that the cells that produced IL-4 in response to in vivo injection of anti-CD3 were highly enriched in CD4pos cells with the phenotype leukocyte cell adhesion molecule-1 (LECAM-1)dull, CD44bright, CD45RBdull, NK1.1pos. Indeed, the small population of CD4pos, NK1.1pos cells had the great majority of the IL-4-producing activity of this population. Injection with Staphylococcal enterotoxin B also caused prompt induction of IL-4 mRNA; the cells that were principally responsible for production also had the phenotype of CD4pos, NK1.1pos. These results suggest that possibility that this rare population of T cells may be capable of secreting IL-4 at the outset of immune responses and thus may act to regulate the pattern of priming of naive T cells, by providing a source of IL-4 to favor the development of T cell helper 2-like IL-4-producing cells.
Yoshimoto
T
T
Laboratory of Immunology, National Institute of Allergy and infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Paul
W E
WE
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology; D000941:Antigens / Q000096:biosynthesis* / Q000276:immunology; D000954:Antigens, Surface; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004247:DNA; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis*; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009928:Organ Specificity / Q000276:immunology; D010641:Phenotype; D014176:Protein Biosynthesis; D011506:Proteins / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
D000906:Antibodies; D000907:Antibodies, Bacterial; D000941:Antigens; D000954:Antigens, Surface; D017252:CD3 Complex; D004768:Enterotoxins; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal; D004247:DNA