First Author | Rulifson IC | Year | 1997 |
Journal | J Immunol | Volume | 158 |
Issue | 2 | Pages | 658-65 |
PubMed ID | 8992981 | Mgi Jnum | J:91779 |
Mgi Id | MGI:3050731 | Doi | 10.4049/jimmunol.158.2.658 |
Citation | Rulifson IC, et al. (1997) CD28 costimulation promotes the production of Th2 cytokines. J Immunol 158(2):658-65 |
abstractText | 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. |