Abstract
It is unclear why immunological control of HIV replication is incomplete in most infected individuals. We examined here the CD8+ T cell response to HIV-infected CD4+ T cells in rare patients with immunological control of HIV. Although high frequencies of HIV-specific CD8+ T cells were present in nonprogressors and progressors, only those of nonprogressors maintained a high proliferative capacity. This proliferation was coupled to increases in perforin expression. These results indicated that nonprogressors were differentiated by increased proliferative capacity of HIV-specific CD8+ T cells linked to enhanced effector function. In addition, the relative absence of these functions in progressors may represent a mechanism by which HIV avoids immunological control.
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Acknowledgements
We thank M. Alston for assistance with cell cycle analysis; M. Rust for editorial assistance; and the patients for their commitment to completion of this project.
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Web Fig. 1.
CD8+ T cell proliferation to HIVSF162-infected CD4+ T cells and purified peptides in an HLA-A*2+B*57+ LTNP and progressor. Pseudocolor density plots showing responses of CD3+CD8+lymphocytes of a representative LTNP (34(A)) and progressor (104(D)). (a) HIV-KAF11 and CMV-NLV9 tetramer+CD8+ T cell proliferation in response to HIV-infected CD4+ T cells. (b,c) HIV- and CMV-specific CD8+ T cell proliferative responses after stimulation with the HIV p24(163-174) KAF11 peptide (b) or the CMV pp65(495-503) NLV9 peptide (c). Numbers in quadrants indicate the percentages of gated CD3+CD8+ lymphocytes. Left margin, patient identifiers. (PDF 303 kb)
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Migueles, S., Laborico, A., Shupert, W. et al. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 3, 1061–1068 (2002). https://doi.org/10.1038/ni845
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DOI: https://doi.org/10.1038/ni845
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