Impaired TCR-mediated induction of Ki67 by naive CD4+ T cells is only occasionally corrected by exogenous IL-2 in HIV-1 infection |
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Authors: | Sieg Scott F Bazdar Douglas A Lederman Michael M |
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Institution: | Department of Medicine, Division of Infectious Diseases, Case Western Reserve University and University Hospitals of Cleveland, Center For AIDS Research, Cleveland, OH 44106, USA. sfs2@po.cwru.edu |
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Abstract: | Perturbations in naive T cell homeostasis and function may play a major role in the immunodeficiency that accompanies HIV infection. By examining naive CD4(+) T cell function on a single cell basis, we provide evidence that these cells have significant qualitative defects in HIV disease. Ki67, a molecule expressed during cell cycle progression, is induced less efficiently among naive CD4(+) T cells from HIV-infected individuals following activation with anti-TCR Ab. The impairment in Ki67 expression is evident even when a separate function, CD62L down-modulation, is within normal ranges. Moreover, the defects in Ki67 induction are only sometimes corrected by the addition of rIL-2 to cell cultures. An initial assessment of IL-2 unresponsiveness in cells from selected HIV-infected individuals suggests that the defect is not a consequence of impaired IL-2R expression or IL-2R signaling capability. Qualitative defects in naive T cells that cannot be routinely corrected by IL-2 have significant implications for disease pathogenesis and for strategies using IL-2 as a vaccine adjuvant in HIV disease. |
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