Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes
Citation: Yang OO, Kalams SA, Rosenzweig M, Trocha A, Jones N, Koziel M, Walker BD, Johnson RP (Sep 1996) Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes. J Virol. (Volume 70(9):5799-806.) (RSS)
Summary: Numerous studies of human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) have examined their ability to recognize B-cell lines expressing recombinant HIV-1 proteins, but relatively few data regarding the lysis of HIV-1-infected cells by CTL are available. We studied the ability of HIV-1-specific CTL clones of defined epitope specificity and HLA restriction to lyse infected CD4+ cells at serial time points following infection. CD4+ cell lines were acutely infected with HIV-1 IIIB at a high multiplicity of infection, and the kinetics of cell lysis were examined and compared with the kinetics of viral replication. Intracellular HIV-1 p24 expression was detected by 1 to 2 days after infection, reaching over 98% positive cells by day 4. Recognition of the infected cells by HLA A2- and B14-restricted CTL clones closely paralleled intracellular p24 expression and preceded peak virion production. The maximal levels of lysis with Gag-, reverse transcriptase-, and envelope-specific clones were different, however. The Gag- and envelope-specific clones lysed infected cells at levels equivalent to peptide-sensitized controls, whereas lysis by the reverse transcriptase-specific clones plateaued at a lower level. Peptide titration curves indicated that this effect was not due to differences in sensitivity to the cognate epitopes for the different clones. Although HIV-1 infection induced an approximately 50% decrease in class I HLA expression on the surface of infected cells, lysis by CTL clones was unaffected. These studies indicate that HIV-1-specific CTL can efficiently lyse HIV-1-infected CD4+ cells and suggest that the partial downregulation of class I molecules in infected cells does not significantly affect recognition by CTL.
This work disputes the findings of source A diffusible lymphokine produced by CD8+ T lymphocytes..
- Finding here: HIV-1-specific CD8+ cytotoxic T lymphocytes efficiently kill infected cells at 100%, early in life cycle, in HLA-restricted fashion.