PERSISTENT HIGH-FREQUENCY OF HUMAN IMMUNODEFICIENCY VIRUS-SPECIFIC CYTOTOXIC T-CELLS IN PERIPHERAL-BLOOD OF INFECTED DONORS

Human immunodeficiency virus (HIV)specific cytotoxic T lymphocytes (CT Ls) are thought to play a major role in the immune response to HIV inf ection, The HIV-specific CTL response is much stronger than previously documented in an infectious disease, yet estimates of CTL frequency d erived from limiting dilution analysis (LDA) are relatively low and co mparable to other viral infections, Here we show that individual CTL c lones specific for peptides from HIV gag and pol gene products are pre sent at high levels in the peripheral blood of three infected patients and that individual CTL clones may represent between 0.2% and 1% of T cells, Previous LDA in one donor had shown a frequency of CTL precurs ors of 1/8000, suggesting that LDA may underestimate CTL effector freq uency, In some donors individual CTL clones persisted in vivo for at l east 5 years, In contrast, in one patient there was a switch in CTL us age suggesting that different populations of CTLs can be recruited dur ing infection, These data imply strong stimulation of CTLs, potentiall y leading some clones to exhaustion.