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Alterations of T-cell receptor variable region expression in human immunodeficiency virus disease
J P McCoy1, W R Overton, L Blumstein
1Department of Pediatrics, Cooper Hospital/University Medical Center, Camden, New Jersey, USA.
Insights
Human immunodeficiency virus (HIV) disease may selectively deplete CD4+ T lymphocytes. This selective loss, particularly of V beta 19+ cells, suggests HIV may encode a superantigen, impacting T-cell receptor diversity.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus (HIV) infection leads to CD4+ T-lymphocyte depletion, a hallmark of disease progression.
- The mechanism of CD4+ T-cell loss, whether random or selective, is crucial for understanding HIV pathogenesis.
- T-cell receptor (TCR) variable beta (V beta) chain expression may influence CD4+ T-cell susceptibility to HIV-induced depletion.
Purpose of the Study:
- To investigate whether CD4+ T-lymphocyte depletion in HIV disease is a selective process.
- To determine if specific T-cell receptor V beta chain expression is associated with CD4+ T-cell loss in HIV+ patients.
- To test the hypothesis that HIV encodes a superantigen responsible for selective T-cell depletion.
Main Methods:
- Analysis of peripheral blood from normal controls and HIV+ patients.
- Utilizing three-color flow cytometry to quantify the expression of V beta 2, V beta 3, V beta 8, V beta 13, and V beta 19 on lymphocytes.
- Stratifying HIV+ patients by absolute CD4+ T-cell counts and Centers for Disease Control (CDC) disease stage.
Main Results:
- Significant alterations in V beta chain expression were observed in HIV+ individuals compared to controls.
- Selective depletion of CD4+ T-lymphocytes expressing the V beta 19 chain was identified.
- These changes in V beta chain profiles correlated with disease stage and CD4+ T-cell counts.
Conclusions:
- The depletion of CD4+ T-lymphocytes in HIV disease appears to be a selective event, not random.
- The findings support the hypothesis that HIV may encode a superantigen, leading to the selective elimination of specific T-cell populations (e.g., V beta 19+).
- Multicolor flow cytometry, combined with patient stratification, is a valuable tool for detecting subtle immunologic changes in HIV infection.
Abstract:
Since only a small percentage of CD4+ lymphocytes is infected at any one time during the course of human immunodeficiency virus (HIV) disease, a question central to the pathogenesis of HIV is whether or not the depletion of CD4+ lymphocytes is a random or selective event. The majority of peripheral blood T lymphocytes use alpha and beta variable chains as components of their T-cell receptor (TCR) complex. Depletion of CD4+ T lymphocytes from the peripheral blood may be dependent on the V beta chain expressed by the CD4+ cell, based on the hypothesis that HIV may encode a superantigen. Peripheral blood from normal controls and HIV+ patients was studied for alterations in the expression of various V beta chains of the TCR. Three-color flow cytometry was used to determine the expression of V beta 2, V beta 3, V beta 8, V beta 13, and V beta 19 on all lymphocytes and on both CD4+ and CD8+ lymphocytes independently. Alteration of the V beta chains in HIV+ disease was analyzed as a function of absolute CD4 count and Centers for Disease Control (CDC) stage of the patient. These data suggest that the loss of T helper (CD4) lymphocytes during the course of HIV disease may be a selective event. These data are consistent with the hypothesis that selective depletion of CD4+, V beta 19+ lymphocytes may be due to the encoding of a superantigen by HIV. Furthermore, using multicolor flow cytometry and stratifying patients by absolute CD4 counts (or stage of disease) may reveal immunologic changes that might otherwise be overlooked.