Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals.

T cell apoptosis has been proposed as an important contributor to the functional defects and depletion of T cells in HIV-infected individuals. However, the mechanisms involved in this apoptosis have not been elucidated. We recently showed that peripheral blood T cells from HIV-infected individuals are especially susceptible to Fas antigen-induced apoptosis. In this study we examine the role of Fas, CTLA-4, tumor necrosis factor (TNF) receptors (TNFR) and CD30, receptors known to be involved in T cell activation-induced cell death (AICD), in the spontaneous and activation (anti-CD3)-induced apoptosis of peripheral blood T cells from asymptomatic HIV-infected individuals. We report here that spontaneous and activation-induced T cell apoptosis cannot be inhibited by reagents that block interactions of Fas, CTLA-4, p55 and p75 TNFR and CD30 with their respective ligands. We also show that IL-12, IFN-gamma, IL-4 and IL-10 cannot modify spontaneous, activation- and anti-Fas-induced apoptosis. Anti-Fas preferentially induced CD4+ T cell apoptosis whereas AICD induced apoptosis equally in CD4+ and CD8+ T cells. We conclude that T cell AICD in HIV infection is not mediated by Fas, thus indicating that Fas-induced and activation-induced T cell apoptosis are independent mechanisms of apoptosis which may play different roles in the pathogenesis of HIV infection.

[1]  E. Lacy,et al.  Surface T cell Fas receptor/CD95 regulation, in vivo activation, and apoptosis. Activation-induced death can occur without Fas receptor. , 1996, Journal of immunology.

[2]  T. Idziorek,et al.  T helper type 1/T helper type 2 cytokines and T cell death: preventive effect of interleukin 12 on activation-induced and CD95 (FAS/APO-1)- mediated apoptosis of CD4+ T cells from human immunodeficiency virus- infected persons , 1995, The Journal of experimental medicine.

[3]  M. Lenardo,et al.  Induction of apoptosis in mature T cells by tumour necrosis factor , 1995, Nature.

[4]  G. Mills,et al.  Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo. , 1995, International immunology.

[5]  P. Krammer,et al.  Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120 , 1995, Nature.

[6]  C. Smith,et al.  Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals , 1995, The Journal of experimental medicine.

[7]  V. Metelev,et al.  Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. , 1995, Science.

[8]  S. Ju,et al.  Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation , 1995, Nature.

[9]  Seamus J. Martin,et al.  Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas , 1995, Nature.

[10]  P. Krammer,et al.  Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) , 1995, Nature.

[11]  T. Curiel,et al.  Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes , 1995, Nature Medicine.

[12]  S. Nagata,et al.  Selective apoptosis of CD4+CD8+ thymocytes by the anti-Fas antibody , 1995, The Journal of experimental medicine.

[13]  J. Gribben,et al.  CTLA4 mediates antigen-specific apoptosis of human T cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  C. Smith,et al.  Fas ligand mediates activation-induced cell death in human T lymphocytes , 1995, The Journal of experimental medicine.

[15]  D. Kraft,et al.  HIV-1-induced thymocyte depletion is associated with indirect cytopathogenicity and infection of progenitor cells in vivo. , 1995, Immunity.

[16]  R. Coffman,et al.  Type 1/type 2 cytokine modulation of T-cell programmed cell death as a model for human immunodeficiency virus pathogenesis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  F. Ramsdell,et al.  Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death. , 1994, International immunology.

[18]  F. Barré-Sinoussi,et al.  Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Tschopp,et al.  Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways , 1994, Nature.

[20]  H Hengartner,et al.  Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. , 1994, Science.

[21]  Z. Darżynkiewicz,et al.  CD4 engagement induces Fas antigen‐dependent apoptosis of T cells in vivo , 1994, European journal of immunology.

[22]  N. Boiani,et al.  Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines , 1994 .

[23]  Terry Farrah,et al.  The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death , 1994, Cell.

[24]  D. Williams,et al.  Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines. , 1994, Blood.

[25]  Takashi Suda,et al.  Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor family , 1993, Cell.

[26]  J. Berzofsky,et al.  Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro. , 1993, Science.

[27]  N. Chirmule,et al.  Accelerated apoptosis in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus type-1 infected patients and in CD4 cross-linked PBMCs from normal individuals. , 1993, Blood.

[28]  F. Ramsdell,et al.  Fas transduces activation signals in normal human T lymphocytes , 1993, The Journal of experimental medicine.

[29]  H. Schuitemaker,et al.  Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants. , 1993, The Journal of infectious diseases.

[30]  N. Copeland,et al.  CD30 antigen, a marker for Hodgkin's lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF , 1993, Cell.

[31]  J. Heeney,et al.  Programmed cell death in AIDS-related HIV and SIV infections. , 1993, AIDS research and human retroviruses.

[32]  N. Haigwood,et al.  Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis , 1992, The Journal of experimental medicine.

[33]  F. Miedema,et al.  Programmed death of T cells in HIV-1 infection. , 1992, Science.

[34]  A. Capron,et al.  Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals , 1992, The Journal of experimental medicine.

[35]  J. Ameisen.  Activation-induced Death by Apoptosis in CD4 + T Cells from Human Immunodeficiency Virus-lnfected Asymptomatic Individuals By Her% Groux,* G6rard Torpier,* Didier Mont6,* Yves Mouton,~ , 1992 .

[36]  Atsushi Hase,et al.  The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis , 1991, Cell.

[37]  P. Möller,et al.  Monoclonal antibody-mediated tumor regression by induction of apoptosis. , 1989, Science.

[38]  S. Yonehara,et al.  A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor , 1989, The Journal of experimental medicine.