Mukherjee, Sambuddho and Ahmed, Asma and Nandi, Dipankar (2005) CTLA4-CD80/CD86 Interactions On Primary Mouse CD4+ T Cells Integrate Signal-Strength Information to Modulate Activation With Concanavalin A. In: Journal of Leukocyte Biology, 78 (1). pp. 144-157.
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The mechanisms by which concanavalin A (Con A), a lectin, activates T cells are poorly studied. A low dose of Con A is stimulatory for T cells, whereas a high dose of Con A results in suppression of proliferation and enhanced T cell death. The expression and functional roles of costimulatory receptors, CD28 and cytotoxic T-lymphocyte antigen 4 (CTLA4), and their ligands, CD80 and CD86, on primary mouse $CD4^+ T$ cells after activation with different doses of Con A were studied. CTLA4-CD80/CD86 interactions in this T:T cell activation model demonstrate distinct outcomes depending on the dose of Con A. CTLA4-CD80/CD86 interactions inhibit $CD4^+ T$ cell cycling and survival after activation with a suppressive dose of Con A by increasing oxidative stress and decreasing levels of BclXL. The enhanced $CD4^+ T$ cell death with a suppressive dose of Con A is dependent on excess $H_2O_2$ and nitric oxide but is independent of Fas and caspase activity. It is surprising that the increased proliferation of $CD4^+ T$ cells with a suppressive dose of Con A on blocking CTLA4-CD80/CD86 interactions is largely interleukin (IL)-2-independent but is cyclosporine A-sensitive. On activation with a stimulatory dose of Con A, CTLA4-CD80/CD86 interactions enhance T cell activation and survival by reducing the production of reactive oxygen species, increasing IL-2 and BclXL levels. Here IL-10 but not transforming growth factor- \beta plays a functional role. In summary, CTLA4-CD80/CD86 interactions on T cells integrate signal strength, based on the dose of Con A, to enhance or inhibit primary mouse $CD4^+ T$ cell cycling and survival.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to The Federation of American Societies for Experimental Biology.|
|Keywords:||costimulation;T cell cycling and survival;IL-2-independent;oxidative stress;IL-10;TGF- beta|
|Department/Centre:||Division of Biological Sciences > Biochemistry|
|Date Deposited:||22 Aug 2005|
|Last Modified:||07 Feb 2012 08:54|
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