Biased dependency of CD80 versus CD86 in the induction of transcription factors regulating the human IL-2 promoter

• Published in: International immunology Vol. 10; no. 4; pp. 499 - 506
• Main Authors: Olsson, C, Michaëlsson, E, Parra, E, Pettersson, U, Lando, P A, Dohlsten, M
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.04.1998
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Antigens, CD - immunology; Antigens, CD - physiology; B7-1 Antigen - immunology; B7-1 Antigen - physiology; B7-2 Antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CHO Cells - metabolism; Cricetinae; Humans; Interleukin-2 - genetics; Lymphocyte Activation - immunology; Membrane Glycoproteins - immunology; Membrane Glycoproteins - physiology; Mice; NF-kappa B - biosynthesis; NF-kappa B - physiology; Nuclear Proteins - biosynthesis; Nuclear Proteins - physiology; Promoter Regions, Genetic; Signal Transduction - drug effects; Signal Transduction - physiology; Superantigens - immunology; Transcription Factor AP-1 - biosynthesis; Transcription Factor AP-1 - physiology; Transcription Factors - biosynthesis; Transcription Factors - physiology; Transcription, Genetic
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/10.4.499

In addition to the signals obtained by ligation of the TCR, T cells need additional, co-stimulatory signals to be activated. One such co-stimulatory signal is delivered when CD28 on T cells binds to CD80 or CD86 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 mainly co-stimulated by CD80. To further characterize the consequences of this biased co-stimulatory dependency, we employed a well-defined system of transfected CHO cells expressing human MHC class II together with 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 but optimal levels with CD80. To analyze IL-2 transcriptional activity in CD80 and CD86 co-stimulated T cells we used Jurkat T cells transfected with luciferase reporter gene constructs. CD80 induced higher levels of IL-2 promoter-enhancer activity compared to CD86. Furthermore, the activity of transcription factors regulating the IL-2 promoter-enhancer region including activation protein-1, CD28 response element and nuclear factor kappaB were 4-8 times higher after CD80 compared to CD86 ligation. Our results suggest that the eventual appearance of CD80 on recently activated CD86+ APC is important for the superinduction of IL-2 production and to support vigorous T cell proliferation.