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.
Department of Microbiology and Immunology, Indiana University School of Medicine and Walther Oncology Center, Indianapolis, USA.
D S
DS
Vinay
B S
BS
Kwon
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