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. 2010 May 15;24(8):1095-105.
doi: 10.1097/QAD.0b013e3283377a1e.

HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses

Rachel E Owen  1 , John W Heitman, Dale F Hirschkorn, Marion C Lanteri, Hope H Biswas, Jeffrey N Martin, Melissa R Krone, Steven G Deeks, Philip J Norris; NIAID Center for HIV/AIDS Vaccine Immunology
Affiliations

HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses

Rachel E Owen et al. AIDS. .

Abstract

Objective: HIV elite controllers are a unique group of rare individuals who maintain undetectable viral loads in the absence of antiretroviral therapy. We studied immune responses in these individuals to inform vaccine development, with the goal of identifying the immune correlates of protection from HIV.

Methods: We compared markers of cellular activation, HIV-specific immune responses and regulatory T (Treg) cell frequencies in four groups of individuals: HIV-negative healthy controls, elite controllers (HIV RNA level <75 copies/ml), individuals on HAART and individuals with HIV RNA level more than 10,000 copies/ml (noncontrollers).

Results: Elite controllers possessed significantly lower levels of activated HIV-specific CD8 T cells and of recently divided HIV-specific CD4 T cells than noncontrollers, whereas these differences were not seen in the respective cytomegalovirus-specific T-cell populations. Elite controllers also mounted a stronger and broader cytokine and chemokine response following HIV-specific stimulation than individuals on HAART and noncontrollers. Finally, we found that HAART-suppressed individuals had elevated Treg cell frequencies, whereas elite controllers and noncontrollers maintained normal percentages of Treg cells.

Conclusion: Elite controllers maintain high levels of HIV-specific immune responses with low levels of HIV-specific T-cell activation and do not have elevated Treg cell levels. Based on these data an ideal HIV vaccine would induce strong HIV-specific immune responses whereas minimizing HIV-specific T-cell activation.

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Figures

Figure 1
Figure 1. Elite controllers have lower levels of activated and recently divided HIV-specific T cells than non-controllers
(a) Representative flow cytometry plots of HIV-specific CD8+ T cells illustrate the gating strategy, showing HIV-specific cells (left panel), recently divided cells in a smoothed histogram of Ki67 expression (middle panel), and activation status by CD38 and HLA-DR co-expression (right panel). (b) The percentage of activated CD4+ IFNγ+ T cells and (c) CD8+ IFNγ+ T cells co-expressing CD38 and HLA-DR following HIV p55 stimulation. (d) The percentage of recently divided CD4+ IFNγ+ Ki67+ T cells and (e) CD8+ IFNγ+ Ki67+ T cells following p55 stimulation. * p<0.05, ** p<0.01.
Figure 2
Figure 2. Elite controllers do not have lower levels of activated and recently divided CMV-specific T cells than non-controllers
(a) The percentage of activated CD4+ IFNγ+ T cells and (b) CD8+ IFNγ+ T cells co-expressing CD38 and HLA-DR following pp65 stimulation. (c) The percentage of recently divided CD4+ IFNγ+ Ki67+ T cells and (d) CD8+ IFNγ+ Ki67+ T cells following pp65 stimulation. *** p<0.001.
Figure 3
Figure 3. Elite controllers mount a broader and stronger cytokine and chemokine response following HIV-specific stimulation than non-controllers
Heat map showing the log10 mean fold-change in cytokines and chemokines following (a) HIV p55 stimulation and (b) CMV pp65 stimulation. Progressive increases in log10 mean fold-change are represented by blue to red colors. Significant p values are indicated by asterisks (* p< 0.05, ** p< 0.001), with a red * representing significant differences between the elite controllers and the non-controllers, a yellow * representing significant differences between the HAART suppressed group and the non-controllers, a blue * representing significant differences between non-controllers and HIV uninfected subjects, and a black * representing significant differences between elite controllers and the HAART suppressed group.
Figure 4
Figure 4. Elite controllers maintain normal numbers of Treg cells
(a) A representative flow cytometry plot of Treg cells is shown to illustrate the gating strategy showing live PBMCs (left panel) gated on CD3+ CD4+ cells (middle panel) and finally on CD25+ cells (right panel). (b) The frequency of Treg cells (CD25+ CD127− CD152+) as a percentage of viable CD3+ CD4+ cells. (c) The absolute number of Treg cells in HIV infected individuals. (d) Correlation between the absolute number of Treg cells and age for all HIV infected individuals. * p<0.05.
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References

    1. Deeks SG, Walker BD. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity. 2007;27:406–416. - PubMed
    1. Hatano H, Delwart EL, Norris PJ, Lee TH, Dunn-Williams J, Hunt PW, et al. Evidence for persistent low-level viremia in individuals who control human immunodeficiency virus in the absence of antiretroviral therapy. J Virol. 2009;83:329–335. - PMC - PubMed
    1. Hunt PW, Brenchley J, Sinclair E, McCune JM, Roland M, Page-Shafer K, et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis. 2008;197:126–133. - PMC - PubMed
    1. Saez-Cirion A, Lacabaratz C, Lambotte O, Versmisse P, Urrutia A, Boufassa F, et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci U S A. 2007;104:6776–6781. - PMC - PubMed
    1. Emu B, Sinclair E, Favre D, Moretto WJ, Hsue P, Hoh R, et al. Phenotypic, functional, and kinetic parameters associated with apparent T-cell control of human immunodeficiency virus replication in individuals with and without antiretroviral treatment. J Virol. 2005;79:14169–14178. - PMC - PubMed

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