Open AccessRole of tumour necrosis factor‐alpha (TNF‐α) in the induction of HIV‐1 gp120‐mediated CD4 + T cell anergy
Author(s) -
KANEKO H.,
HISHIKAWA T.,
SEKIGAWA I.,
HASHIMOTO H.,
OKUMURA K.,
KANEKO Y.
Publication year - 1997
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1997.4231325.x
Subject(s) - immunology , tumor necrosis factor alpha , human immunodeficiency virus (hiv) , medicine , necrosis , biology , pathology
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 G 1 (G 1A ) 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 p56 lck 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.