BIASED DEPENDENCY OF CD80 VERSUS CD86 IN THE INDUCTION OF TRANSCRIPTION FACTORS REGULATING THE HUMAN IL-2 PROMOTER

In addition to the signals obtained by ligation of the TCR, T cells ne ed additional, co-stimulatory signals to be activated. One such co-sti mulatory signal is delivered when CD28 on T cells binds to CD80 or CD8 6 on antigen-presenting cells (APC). In the present study, we analyzed the ability of CD80 and CD86 to co-stimulate human T cells activated by superantigen. Using the Raji B cell lymphoma, which express similar levels of CD80 and CD86, it was found that T cell proliferation was m ainly cc-stimulated by CD80. To further characterize the consequences of this biased costimulatory dependency, we employed a well-defined sy stem of transfected CHO cells expressing human MHC class II together w ith CD80, CD86 or CD80 and CD86. Proliferation of freshly prepared CD4 (+) T cells required the presence of either CD80 or CD86. However, IL- 2 production reached only suboptimal levels in the presence of CD86 bu t optimal levels with CD80. to analyze IL-2 transcriptional activity i n CD80 and CD86 co-stimulated T cells we used Jurkat T cells transfect ed with luciferase reporter gene constructs. CD80 induced higher level s of IL-2 promoter-enhancer activity compared to CD86. Furthermore, th e activity of transcription factors regulating the IL-2 promoter-enhan cer region including activation protein-1, CD28 response element and n uclear factor kappa B were 4-8 times higher after CD80 compared to CD8 6 ligation. Our results suggest that the eventual appearance of CD80 o n recently activated CD86(+) APC is important for the superinduction o f IL-2 production and to support vigorous T cell proliferation.