Apoptotic cell death and cytokine dysregulation in human immunodeficiency virus infection: pivotal factors in disease progression

Abstract

The progressive loss of CD4 T lymphocyte is patognomonic of Human Immunodeficiency Virus (HIV) infection and results in immunodeficiency and the appearance of acquired immunodeficiency syndrome (AIDS)-defining pathologies. Although a percentage of CD4 T lymphocytes is destroyed directly by HIV infection, a much higher proportion of lymphocytes remains uninfected and therefore must be destroyed by mechanisms not directly involving viral infection. One such mechanism is apoptotic T cell death (ATCD). ATCD in HIV infection has been shown to be: 1) secondary to cross-linking of CD4 by viral proteins; 2) mediated by both APO-1/Fas and lymphotoxin (LT); and 3) differentially modulated by type 1 and type 2 cytokines. We will briefly analyze the experimental evidences suggesting that ATCD contributes significantly to the immunopathogenesis of HIV/AIDS via depletion of CD4 + T cells.

Correlation of immune activation with HIV-1 RNA levels assayed by real-time RT-PCR in HIV-1 subtype C infected patients in Northern India

“…However, assaying CD4+ T cell numbers alone is inadequate for HIV monitoring, since the normal T lymphocyte reference range of the study population has enormous variation due to age, sex, and other factors (Amatya et al, 2004;McCune, 2001). The PVL provide an accurate measure to identify new infections, monitor disease progression and response to ART (Clerici et al, 1997;Ho et al, 1995;Katzenstein and Holodniy, 1995;Wei et al, 1995). Chronic immune activation detected by the co-expression of CD38 and HLA-DR on CD4+ and CD8+ T-cells correlates with disease progression (Clerici et al, 1997;Swanson et al, 2005).…”

“…The PVL provide an accurate measure to identify new infections, monitor disease progression and response to ART (Clerici et al, 1997;Ho et al, 1995;Katzenstein and Holodniy, 1995;Wei et al, 1995). Chronic immune activation detected by the co-expression of CD38 and HLA-DR on CD4+ and CD8+ T-cells correlates with disease progression (Clerici et al, 1997;Swanson et al, 2005). These parameters have not been well defined in HIV-1 C infection.…”

Neuroimmunity and the Blood–Brain Barrier: Molecular Regulation of Leukocyte Transmigration and Viral Entry into the Nervous System with a Focus on NeuroAIDS

“…Comorbid clinical depression and some symptoms of AIDS are similar, such as poor appetite, weight loss, and cognitive impairment. It has been shown that inflammatory cytokines can contribute to these symptoms (Dantzer and Kelley 1989;Clerici et al 1997). …”

Interleukin-15 is a potent survival factor in the prevention of spontaneous but not CD95-induced apoptosis in CD4 and CD8 T lymphocytes of HIV-infected individuals. Correlation with its ability to increase BCL-2 expression

“…While apoptosis plays essential roles in immune regulation, it can be pathogenic where it interferes with the generation and renewal of effector cells, as appears to be the case in HIV infection. 10,11 The causes of lymphocyte apoptosis in HIVinfected individuals are multi-factorial and are believed to include TCR/CD3 triggering in the absence of appropriate co-stimulation, CD95-CD95 ligand interactions and gp120-CD4 interactions. 10,11 In addition, alterations in the profile of cytokine production and deprivation of growth factors arising from deletion of lymphocyte populations can contribute to further lymphocyte loss.…”

“…10,11 The causes of lymphocyte apoptosis in HIVinfected individuals are multi-factorial and are believed to include TCR/CD3 triggering in the absence of appropriate co-stimulation, CD95-CD95 ligand interactions and gp120-CD4 interactions. 10,11 In addition, alterations in the profile of cytokine production and deprivation of growth factors arising from deletion of lymphocyte populations can contribute to further lymphocyte loss. 11,12 Freshly isolated lymphocytes of HIV-infected individuals are highly susceptible to apoptosis following short-term culture in the absence of exogenous cytokines, commonly referred to as spontaneous apoptosis, and to apoptosis induced in vitro by mitogens, recall antigens and monoclonal antibodies (mAbs) directed against the CD3 and CD95 molecules.…”