CD28 costimulation promotes the production of Th2 cytokines.
CD28 ligation augments TCR-mediated proliferation, IL-2 production, and T cell survival. However, the role of CD28 costimulation in T cell differentiation remains controversial. To address this issue, CD28+ and CD28-deficient TCR alphabeta transgenic (Tg) mice were used to examine cytokine production by T cells following antigenic stimulation. Increasing CD28 ligation resulted in increased production of IL-4 and IL-5, consistent with differentiation toward a Th2 phenotype, in both CD4+ TCR Tg T cells and CD8+ TCR Tg T cells. The same result was obtained with CD4+ TCR Tg mice bred to RAG2-deficient mice, indicating that the Th2 differentiation observed with increased CD28 ligation was not due to the presence of memory T cells. Although CD28 costimulation is an essential factor regulating IL-2 synthesis, differentiation toward a Th2-like phenotype by CD28 ligation was not an indirect effect of enhanced IL-2 production. In contrast, blockade of IL-4 during the primary cultures of the T cells resulted in a profound inability to produce Th2-type cytokines upon restimulation. The critical role of IL-4 was confirmed by the finding that CD28-deficient TCR alphabeta Tg+ T cells cultured with rIL-4 differentiated into Th2-like T cells. Therefore, CD28 ligation promotes the production of Th2-type cytokines by naive murine T cells via an IL-4-dependent mechanism.
Rulifson
I C
IC
Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, IL 60637, USA.
Sperling
A I
AI
Fields
P E
PE
Fitch
F W
FW
Bluestone
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta