Details

Autor(en) / Beteiligte

• Elloso, M. Merle
• Scott, Phillip

Titel

Differential requirement of CD28 for IL‐12 receptor expression and function in CD4+ and CD8+ T cells

Ist Teil von

• European journal of immunology, 2001-02, Vol.31 (2), p.384-395

Ort / Verlag

Weinheim: WILEY‐VCH Verlag GmbH

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• IL‐12 is a potent inducer of IFN‐γ production and Th1 responses. Co‐stimulation mediated by B7 has been shown to synergize with IL‐12 for optimal IFN‐γ production and proliferation in vitro. In this study, we examined the requirement of CD28 / B7 interactions for optimal induction of IL‐12 receptor(R) β1 and β2 expression and IFN‐γ. IL‐12‐induced IFN‐γ production and STAT4 nuclear translocation were markedly reduced in CD28– / – splenocytes compared to that of wild‐type (WT) splenocytes. Analysis of IL‐12R expression revealed that IL‐12 induced similar levels of IL‐12R β2 mRNA expression in WT and CD28– / – cells. In contrast, IL‐12R β1 expression was impaired in CD28– / – cells, indicating that expression of IL‐12R β1 and β2 is differentially regulated by CD28. CD28– / – CD4+ but not CD8+ cells exhibited a defect in IL‐12Rβ1 expression that was associated with a marked decrease in IL‐12 binding as well as IL‐12‐induced IFN‐γ production. IL‐2 could restore IL‐12R expression to CD28– / – CD4+ cells, however, this occurred independently of IL‐2‐induced proliferation. Thus, these findings identify distinct requirements for CD28 in the capacity of CD4+ and CD8+ cells to respond maximally to IL‐12.