Immune dysregulation and CD4+ T cell loss in HIV-1 infection (original) (raw)
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CD4+ T-cell depletion in HIV infection: Are we closer to understanding the cause
Nature Medicine, 2002
The cause of the progressive depletion of CD4 + T cells in HIV-infected people is one of the most fundamental and controversial issues in AIDS research. HIV infects and kills CD4 + T cells. The infection results in high T-cell activation and turnover. An immediately intuitive assumption is that HIV-mediated destruction of CD4 + cells directly reduces the number of these cells and that the high turnover rates of T cells and the slow progression to AIDS reflect a long, but eventually lost struggle of the immune system to replace killed cells in its effort to maintain T-cell homeostasis 1-4 .
CD4+ T Cell Depletion in Human Immunodeficiency Virus (HIV) Infection: Role of Apoptosis
Viruses, 2011
Human immunodeficiency virus (HIV) infection is principally a mucosal disease and the gastrointestinal (GI) tract is the major site of HIV replication. Loss of CD4 + T cells and systemic immune hyperactivation are the hallmarks of HIV infection. The end of acute infection is associated with the emergence of specific CD4+ and CD8+ T cell responses and the establishment of a chronic phase of infection. Abnormal levels of immune activation and inflammation persist despite a low steady state level of viremia. Although the causes of persistent immune hyperactivation remain incompletely characterized, physiological alterations of gastrointestinal tract probably play a major role. Failure to restore Th17 cells in gut-associated lymphoid tissues (GALT) might impair the recovery of the gut mucosal barrier. This review discusses recent advances on understanding the contribution of CD4 + T cell depletion to HIV pathogenesis.
Immunologic Targets of HIV Infection: T Cells
Annals of the New York Academy of Sciences, 1993
One of the principal targets of human immunodeficiency virus-1 (HIV-I) is the human T lymphocyte (T cell) owing to tropism of the glycoprotein (gp) 160 for the CD4' molecule on the helper T cell (CD4' cell).'.' The best documented surrogate marker of clinical disease progression, decline in CD4+ cell count, has been shown to predict the stage of illness in adults with HIV-I. It is now well known that following an early viremic a prolonged stage of viral latency exists (at least within the peripheral blood compartment), lasting up to 10 years in adults infected by HIV.' Invariably, however, when the CD4' cell count begins to decline, there is a substantial decline in health experienced in patients, usually in the form of opportunistic infections and cancers. In children, the period of latency is shorter and symptomatic infants usually expire by 3 years of age.6 Multiple pathologic mechanisms are thought to contribute to CD4+ cell death: programmed cell death (apoptosis),' antibody and complement-mediated cyto
In this review, immune response and possible causes of depletion of CD4+ T-cell counts in patients with human immunodeficiency (HIV)-1 infection, have been documented. HIV has been recognized as a global problem; however, the developing countries are the most affected by epidemic diseases. Countries in the sub-Saharan Africa seem to bear the bulk of the HIV burden among the developing countries with about 24.7 million ( 63%) of all people living with HIV globally in 2006. The major factor obstructing progress towards an effective vaccine to prevent or modulate HIV - 1 infection is that the critical features needed for a protective immune response are not fully understood. Although, it has been found that potent neutralizing antibodies can protect against experimentally acquired HIV infection in animal models, they are scarcely generated in vivo in the infected person and neutralization resistant viral variants have been monitored to develop rapidly in chronic infection. It is generally believed that cellular immune responses, particularly specific cytotoxic T lymphocytes (CTL), are significant in the host response to HIV - 1 infection. Scientists have observed that CTL develop very early in acute HIV - 1 infection, coincident with a rapid fall in plasma vireamia, whereas in chronic infection their levels are inversely related to viral load. However the potent HIV-specific CTL response ultimately fails to control HIV replication. This could be as a consequence of the emergence of viral variants that escape CTL recognition or impairment.of CTL function.
Increased Turnover of T Lymphocytes in HIV-1 Infection and Its Reduction by Antiretroviral Therapy
Journal of Experimental Medicine, 2001
The mechanism of CD4 ϩ T cell depletion in human immunodeficiency virus (HIV)-1 infection remains controversial. Using deuterated glucose to label the DNA of proliferating cells in vivo, we studied T cell dynamics in four normal subjects and seven HIV-1-infected patients naive to antiretroviral drugs. The results were analyzed using a newly developed mathematical model to determine fractional rates of lymphocyte proliferation and death. In CD4 ϩ T cells, mean proliferation and death rates were elevated by 6.3-and 2.9-fold, respectively, in infected patients compared with normal controls. In CD8 ϩ T cells, the mean proliferation rate was 7.7-fold higher in HIV-1 infection, but the mean death rate was not significantly increased. Five of the infected patients underwent subsequent deuterated glucose labeling studies after initiating antiretroviral therapy. The lymphocyte proliferation and death rates in both CD4 ϩ and CD8 ϩ cell populations were substantially reduced by 5-11 weeks and nearly normal by one year. Taken together, these new findings strongly indicate that CD4 ϩ lymphocyte depletion seen in AIDS is primarily a consequence of increased cellular destruction, not decreased cellular production.