Role of tumour necrosis factor-alpha (TNF-α) in the induction of HIV-1 gp120-mediated CD4+ T cell anergy

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Abstract
The HIV‐1 envelope glycoprotein (gp120) is known to induce antigen‐specific and non‐specific CD4+ T cell anergy. We found that early T cell activation, as indicated by HLA‐DP expression in the early G1 (G1A) phase of the cell cycle, and the inhibition of mitogen‐mediated IL‐2 production induced by gp120, required TNF‐α produced by gp120‐stimulated macrophages. In the presence of an antibody to TNF‐α, these changes induced by gp120 were inhibited, while recombinant TNF‐α induced similar abnormalities of CD4+ T cells, even in the absence of gp120. On the other hand, inhibition of the mixed lymphocyte reaction (MLR) in CD4+ T cells by gp120, which may be related to gp120‐mediated down‐regulation of CD4 expression on T cells and activation of protein tyrosine kinase p56lck in CD4+ T cells, was observed even in the absence of macrophage‐derived TNF‐α induced by gp120. These observations indicate that both TNF‐α‐dependent and independent events contribute to gp120‐mediated CD4+ T cell anergy, and TNF‐α appears to play an important role in inducing CD4+ T cell anergy in HIV‐1 infection.

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