Reduced Immune Activation and T Cell Apoptosis in Human Immunodeficiency Virus Type 2 Compared with Type 1: Correlation of T Cell Apoptosis with β₂Microglobulin Concentration and Disease Evolution

Abstract

This study analyzes the degree of immune activation and characterizes apoptosis in lymphocytes from healthy West African donors or patients infected with human immunodeficiency virus (HIV)-1 or -2. The lower decline of CD4 T cells in HIV-2- compared with HIV-1-infected donors is associated with lower levels of immune activation, evaluated by HLA-DR expression on lymphocytes and sera concentrations of IgG and beta2 microglobulin (beta2m). Ex vivo apoptosis was found in both infections in all lymphocyte subsets, including CD4 and CD8 T cells, as well as B cells, but was lower in HIV-2 than in HIV-1 infection. Interestingly, high correlations were found in HIV-2- and HIV-1-infected donors between the level of CD4 T cell apoptosis and beta2m concentration and progression of the disease. These observations support the hypothesis that long-term activation of the immune system, weaker in HIV-2 infection, significantly contributes to T cell deletion and disease evolution.

Primary Sooty Mangabey Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2nefAlleles Modulate Cell Surface Expression of Various Human Receptors and Enhance Viral Infectivity and Replication

“…HIV-2 is less pathogenic than HIV-1, the major causative agent of AIDS (37,44). Concordant with our data, it has been demonstrated that the levels of immune activation are relatively low in HIV-2 infection (38). TCR-mediated T-cell activation (56).…”

Nef-Mediated Enhancement of Virion Infectivity and Stimulation of Viral Replication Are Fundamental Properties of Primate Lentiviruses

“…It is well established that HIV-2 causes lower levels of immune activation and T-cell apoptosis and is usually less pathogenic than HIV-1 (40,42,43,44,51,52,77). One possible reason for the different virulence in the same human host is that HIV-2 is frequently capable of downmodulating TCR-CD3 to suppress T-cell activation and programmed cell death, whereas HIV-1 is unable to perform this protective function (48,62).…”

Apoptosis in SIV infection

“…54 It has been reported that the low pathogenicity of HIV-2 is associated with a lower immune activation and a lesser degree of CD4 T-cell apoptosis. 55 Importantly, the magnitude of CD4 þ T-cell apoptosis observed in HIV-infected individuals correlates well with the stage of HIV disease. [56][57][58][59][60][61] In addition, changes in the levels of T-cell apoptosis after highly active antiretroviral therapy (HAART) predict the immunological response (i.e., increase in CD4 T-cell count), thus confirming the link between disease progression and apoptosis.…”