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Modulation of cell cycle progression by CTLA4-CD80/CD86 interactions on $CD4^+T$ cells depends on strength of the CD3 signal: critical role for IL-2

Mukherjee, Sambuddho and Ahmed, Asma and Malu, Shruti and Nandi, Dipankar (2006) Modulation of cell cycle progression by CTLA4-CD80/CD86 interactions on $CD4^+T$ cells depends on strength of the CD3 signal: critical role for IL-2. In: Journal of Leukocyte Biology, 80 (1). pp. 66-74.

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Abstract

Cytotoxic T-lymphocyte antigen 4 (CTLA4) is a well-studied T cell costimulatory receptor that is known to inhibit T cell activation. In this study, the relationship between strength of the first signal and costimulatory interactions on primary mouse $CD4^+$ T cells was investigated. CTLA4-CD80/CD86 interactions differentially modulate T cell cycling based on the mode of CD3 signal: Activation with plate-bound (pb) anti-CD3 generates a strong signal compared with a weak signal with soluble (sol) anti-CD3, resulting in approximately sevenfold higher amounts of interleukin (IL)-2 and an increase in cell cycling. Activation of T cells with sol anti-CD3 (weak signal) together with CTLA4-CD80/CD86 blockade lowers IL-2 production and cell cycling, demonstrating an enhancing role for these interactions. Conversely, blockade of CTLA4-CD80/CD86 interactions on T cells activated with pb anti-CD3 (strong signal) increases proliferation, which is consistent with CTLA4 as a negative regulator. Also, coculture of T cells with Chinese hamster ovary cells expressing CD80 or CD86 demonstrates that the strength of the primary signal plays an important role. It is important that modulation of IL-2 amounts leads to distinct alterations in the functional effects of CTLA4-CD80/CD86 interactions. On increasing IL-2 amounts, activation of T cells stimulated with sol anti-CD3 (weak signal) and CTLA4-CD80/CD86 blockade is greater compared with control. Concurrently, neutralization of IL-2 greatly reduces activation of T cells stimulated with pb anti-CD3 (strong signal) and CTLA4-CD80/CD86 blockade compared with control. These results underscore the importance of strength of first signal, CTLA4-CD80/CD86 interactions, and IL-2 amounts in modulating primary $CD4^+$ T cell responses.

Item Type: Journal Article
Additional Information: Copright of this article belongs to Society for Leukocyte Biology
Keywords: T cell activation;Costimulation;cell cycle progression
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 06 Mar 2007
Last Modified: 27 Aug 2008 12:34
URI: http://eprints.iisc.ernet.in/id/eprint/9585

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