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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Reciprocal alterations of Th1/Th2 function in gammadelta T-cell subsets of human immunodeficiency virus-1-infected
Thomas S Dobmeyer1, Rita Dobmeyer, Daniela Wesch
1Department of Medicine III, University Hospital, Frankfurt, Germany.
While T cells that express Vgamma9 as a variable T-cell receptor chain dominate among peripheral blood gammadelta T cells in healthy adults, Vdelta1 cells are the major subpopulation of gammadelta T cells in human immunodeficiency virus (HIV)-infected patients. We used intracellular cytokine staining and flow cytometry to analyse whether an imbalance of T helper 1 (Th1)/T helper 2 (Th2) cytokine patterns, as observed in alphabeta T cells, also occurs in gammadelta T cells. When compared with healthy HIV-negative subjects, HIV+ patients had a decreased number of interferon-gamma (IFN-gamma)+gammadelta T cells, which showed a linear relation to the CD4+ cell count but not to the plasma viral load. Similar results were obtained when Vgamma9 cells were analysed. In contrast, in the Vdelta1 subpopulation, the number of IFN-gamma+ cells was increased in HIV+ donors when compared with healthy subjects. Even though less impressive, the number of interleukin 4 (IL-4)- and IL-10-producing cells was uniformly inversely correlated with the number of tumour necrosis factor-alpha+ and IFN-gamma+ cells. The increased IFN-gamma-producing capacity of Vdelta1 cells might represent a compensatory mechanism for the progressive loss of Vgamma9 gammadelta T cells during the course of HIV infection.
While T cells that express Vgamma9 as a variable T-cell receptor chain dominate among peripheral blood gammadelta T cells in healthy adults, Vdelta1 cells are the major subpopulation of gammadelta T cells in human immunodeficiency virus (HIV)-infected patients. We used intracellular cytokine staining and flow cytometry to analyse whether an imbalance of T helper 1 (Th1)/T helper 2 (Th2) cytokine patterns, as observed in alphabeta T cells, also occurs in gammadelta T cells. When compared with healthy HIV-negative subjects, HIV+ patients had a decreased number of interferon-gamma (IFN-gamma)+gammadelta T cells, which showed a linear relation to the CD4+ cell count but not to the plasma viral load. Similar results were obtained when Vgamma9 cells were analysed. In contrast, in the Vdelta1 subpopulation, the number of IFN-gamma+ cells was increased in HIV+ donors when compared with healthy subjects. Even though less impressive, the number of interleukin 4 (IL-4)- and IL-10-producing cells was uniformly inversely correlated with the number of tumour necrosis factor-alpha+ and IFN-gamma+ cells. The increased IFN-gamma-producing capacity of Vdelta1 cells might represent a compensatory mechanism for the progressive loss of Vgamma9 gammadelta T cells during the course of HIV infection.
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