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HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors

Nature Immunology volume 3, pages 1061–1068 (2002)Cite this article

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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Figure 1: HIV-specific CD8+ T cell responses.
Figure 2: Differences in HIV-specific CD8+ T cell proliferation between HLA-B*57+ LTNPs and progressors.
Figure 3: IFN-γ and perforin expression in CD8+ T cells after stimulation.
Figure 4: Perforin expression of HIV-KAF11 tetramer+CD8+ lymphocytes before and after stimulation in a representative HLA-B*57+ LTNP and two HLA-B*57+ progressors.
Figure 5: CD8+ T cell proliferation and cell cycle analysis after stimulation with anti-CD3 and anti-CD28.

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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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Authors and Affiliations

  1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Stephen A. Migueles, Alisha C. Laborico, W. Lesley Shupert, M. Shirin Sabbaghian, Claire W. Hallahan, Mary McLaughlin, Linda Ehler, Julia Metcalf, Shuying Liu & Mark Connors

  2. Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA

    Ronald Rabin

  3. Department of Clinical Viro-Immunology, CLB Sanquin, Amsterdam, The Netherlands

    Debbie Van Baarle, Stefan Kostense & Frank Miedema

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Correspondence to Mark Connors.

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Supplementary information

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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