Lack of correlation between phenotype activation markers of CD8 lymphocytes and cytotoxic T lymphocyte (CTL) function in HIV-1 infection: evidence for rescue with rIL-2.
CTL activity against HIV-1 antigens expressed on HLA-A-matched EBV-transformed B target cells was detected in 33% (6/18) of freshly isolated PBMC (FPBMC) from patients in the early stages of HIV-1 infection (CDCII). No CTL activity was detected in FPMBC in patients with AIDS (CDCIV). However, the presence of CTL activity did not correlate with the expression of CTL activation markers. A dual-color flow cytometric examination revealed that the CD8+ lymphocytes bearing the memory (CD29) and activation (S6F1) surface molecules increased in number as the HIV-1 infection progressed. This functional and phenotypic discrepancy in memory CD8+ lymphocytes suggests that the memory CD8+ lymphocytes have lost cytotoxic function and become "paralyzed" as the HIV disease progresses. Incubation of PBMC of HIV(+) patients with rIL-2 reactivated predominantly HIV-specific CTL. However, rIL-2 stimulation also activated a "polyclonal or polyreactive" cytotoxic function. The reactivation of CTL function is rIL-2 dosage dependent and the amount of rIL-2 required for reactivation is associated with the severity of the disease. HIV antigen specific CTL in HIV(+) patients can be selectively expanded by HIV antigen stimulation in the presence of rIL-2. These results suggest that the in vivo IL-2 deficiency occurring in HIV-1 infection may be responsible in part for the "paralysis" of HIV specific CTL activity. Such activity can be rescued nonspecifically by exogenous rIL-2 stimulation and expanded specifically by HIV-1 antigen stimulation.
Department of Microbiology, University of Toronto, Ontario, Canada.
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D000954:Antigens, Surface / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000954:Antigens, Surface; D015488:HIV Antigens; D015234:HLA-A Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins