Relative abilities of 4-1BB (CD137) and CD28 to co-stimulate the response of cytokine deflected Th1 and Th2 cells.
In this report we show that allo-stimulated naïve CD4+ cells when cultured in IL-2, IFN-gamma, IL-12 and anti-IL-4 differentiated into Th1 cells expressing very low amounts of 4-1BB molecule, but high amounts of CD28. By contrast, allo-stimulated naive CD4+ cells cultured in the presence of exogenous IL-2, IL-10, IL-4 and anti-INF-gamma evolved into Th2 expressing high amounts of both 4-1BB and CD28. Various Th1/Th2 clones derived from limiting dilution also exhibited similar expression pattern. This differential expression of co-stimulatory molecules on Th subsets account for the ability of 4-1BB to trigger both the proliferation and production of IL-4 by Th2 cells only and for the ability of CD28 to trigger proliferation and typical secretion in both Th1 and Th2 cells.
Vinay
D S
DS
Department of Microbiology and Immunology, Indiana University School of Medicine and Walther Oncology Center, Indianapolis, USA.
Kwon
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9