Pathophysiology of CD4+ T-Cell Depletion in HIV-1 and HIV-2 Infections (original) (raw)
Related papers
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 .
The causal relationships among CD4 cell depletion, HIV replication, and immune activation are not well understood. HIV-2 infection, "nature's experiment" with inherently attenuated HIV disease, provides additional insights into this issue. We report the finding that in HIV-2 and HIV-1 patients with a comparable degree of CD4 depletion the imbalance in the relative sizes of the naive and memory T cell populations and the up-regulation of CD4 and CD8 cell activation markers (HLA-DR, CD38, CD69, Fas molecules) are similar, even though the viral load in the plasma of HIV-2-infected patients is two orders of magnitude lower than in HIV-1 patients and HIV-2 patients are known to have slower rates of CD4 T cell decline and a better clinical prognosis.
Current HIV/AIDS reports, 2006
HIV infection provides a unique challenge to the immune system. CD4+ T cells are targets of infection, whereas effective anti-HIV CD4+ T-cell responses are essential for sustained viral control. There is increasing evidence of preferential depletion of certain subsets of CD4+ T cells. Studies of tissues have demonstrated preferential depletion of CD4+ T cells from gastrointestinal lymphoid tissue (GALT). Simian immunodeficiency virus infection of macaques results in extensive depletion of CD4+ memory T cells from GALT within weeks of infection. Other macaque studies suggest this rapid, profound depletion is generalized across all lymphoid tissue. Although these models provide insight into possible pathogenic processes, these results cannot be directly extrapolated to HIV infection in humans. Although there is depletion of CD4+ T cell memory cells early in HIV infection, the mechanism of this depletion appears to be related to increased cell turnover, chronicity of antigen exposure, ...
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.
Maintenance of HIV-Specific CD4+ T Cell Help Distinguishes HIV-2 from HIV-1 Infection
The Journal of Immunology, 2006
Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4 ؉ T cell count and a strong HIV-specific CD4 ؉ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a crosssectional study of HIV Gag-specific T cell function in HIV-1-and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4 ؉ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57 ؊ ), and more frequently produced IFN-␥ or IL-2 than CD4 ؉ T cells from