Open AccessDecreased CD40 ligand induction in CD4 T cells and dysregulated IL‐12 production during HIV infection
Author(s) -
Guido Vanham,
Lieve Penne,
J. Devalck,
Luc Kestens,
Robert Colebunders,
Eugène Bosmans,
Kris Thielemans,
Jan L. Ceuppens
Publication year - 1999
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.1365-2249.1999.00987.x
Subject(s) - cd40 , cd80 , cd28 , immunology , biology , t cell , antigen , priming (agriculture) , interferon gamma , receptor , il 2 receptor , interleukin 12 , cytokine , immune system , cytotoxic t cell , in vitro , biochemistry , botany , germination
During HIV infection various cytokines are overproduced in early stages, whereas in advanced disease cytokines of the T helper 1 type (e.g. interferon‐gamma (IFN‐γ)) are selectively deficient. During antigenic stimulation, the production of type‐1 cytokines is enhanced by IL‐12, secreted by antigen‐presenting cells (APC) after their interaction with activated CD4 T cells. Two factors are essential in this process: priming APC with IFN‐γ and triggering the CD40 receptor on APC by CD40 ligand (CD40L). In view of the importance of this pathway, we compared its regulation in HIV‐infected and control subjects. After cross‐linking of the T cell receptor (TCR)/CD3 complex, the proportional expression of CD40L was similar on CD4 + T cells from controls and from patients with high circulating CD4 T counts (> 500/μl), but CD40L up‐regulation was significantly reduced in patients with more advanced disease. Simultaneous triggering of the costimulatory receptor CD28 on T cells through its natural ligand CD80 partly corrected the CD40L defect in patients with intermediate CD4 T counts (200–500), but not in AIDS patients. Early production of IFN‐γ was preserved in lymphocytes from HIV + patients. The expression of CD40 on peripheral monocytes from HIV + subjects was increased in a disease stage‐related fashion. Stimulation of mononuclear cells through cell‐bound CD40L and soluble IFN‐γ induced significantly higher IL‐12 in cultures from patients with > 200 circulating CD4 T cells, whereas IL‐12 production was marginally decreased in cultures from patients with < 200 CD4 T cells, compared with healthy control cultures. In conclusion, our data suggest that impaired CD40L induction on CD4 T cells contributes to deficient type‐1 responses through decreased IL‐12 production in AIDS infection, whereas enhanced CD40‐mediated IL‐12 production in less advanced stages might contribute to increased levels of various cytokines in early disease