Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy

Katlama, Christine; Carcelain, Guislaine; Duvivier, Claudine; Chouquet, Cécile; Tubiana, Roland; M, De Sa; Zagury, L; Calvez,; Autran, Brigitte; Costagliola, Dominique; Ilstim,

doi:10.1097/00002030-200210180-00007

Cited by 67 publications

(43 citation statements)

References 4 publications

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“…However, if the primary role of IL-2 is to promote tolerance, the outcome of these trials may to some degree reflect the consequence of manipulating the Treg compartment. IL-2 therapy resulted in a sustained increase in CD4 T-cell counts for most patients (19,70,125), and the effect appeared to be long lasting as shown by 10-year follow-up studies (75). In a pooled retrospective analysis of IL-2 given intravenously, plasma HIV RNA levels were significantly lower in IL-2-treated patients than in patients receiving antiretroviral therapy only (32).…”

Section: Foxp3 In Human Cells Similar To Results With Scurfy and Foxp3mentioning

confidence: 99%

Natural Regulatory T Cells and Persistent Viral Infection

Gowans

Chougnet

et al. 2008

J Virol

138

114

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Section: Foxp3 In Human Cells Similar To Results With Scurfy and Foxp3mentioning

confidence: 99%

Natural Regulatory T Cells and Persistent Viral Infection

Gowans

Chougnet

et al. 2008

J Virol

138

114

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“…This is particularly pertinent to studies of IL-2 treatment in HIV infection. Because IL-2 is generally used to reconstitute the immune system, most reports from clinical trials in HIV infection focus on its effect on CD4 ϩ T cell numbers (56,57). However, CD8…”

Section: Discussionmentioning

confidence: 99%

IL-2 Regulates Perforin and Granzyme Gene Expression in CD8+ T Cells Independently of Its Effects on Survival and Proliferation

Janas

Groves

Kienzle

et al. 2005

The Journal of Immunology

119

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Perforin and the serine protease granzymes are key effectors of CD8+ T cell granule-mediated cytotoxicity, but the requirements for their expression remain largely undefined. We show in this study that IL-2 increased the expression of perforin and granzyme A, B, and C mRNA; intracellular granzyme B protein levels; and cytolytic function in a dose-dependent manner during primary activation of murine CD8+ T cells in vitro. Two approaches showed that these responses were not a consequence of the effects of IL-2 on cell survival and proliferation. First, IL-2 enhancement of perforin and granzyme expression was equivalent in CD8+ T cells from wild-type and bcl-2 transgenic mice, although only the latter cells survived in low concentrations or the absence of added IL-2. This property of bcl-2 transgenic T cells also allowed the demonstration that induction of granzyme A, B, and C mRNA and granzyme B protein required exogenous IL-2, whereas induction of perforin and IFN-γ expression did not. Second, analysis of perforin and granzyme mRNA levels in cells separated according to division number using the dye CFSE showed that the effects of IL-2 were unrelated to division number. Together, these findings indicate that IL-2 can directly regulate perforin and granzyme gene expression in CD8+ T cells independently of its effects on cell survival and proliferation.

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“…Even though there is not yet evidence for decreased IL-2 production by HIV-specific CD8þ T cells, there are several reports indicating that HIV-specific CD4þ T cells progressively lose their ability to produce IL-2 [Clerici et al, 1989;Fauci, 1993;Iyasere et al, 2003;Younes et al, 2003]. In addition, defective IL-2 production by CD8þ T cells has been observed in the LCMV model [Wherry et al, 2003a]; (2) IL-2 upregulated the IL-2 receptor on HIV-specific CD8þ T cells thus enabling them to be more responsive to limited amounts of IL-2 in the environment; (3) the addition of IL-2 reconstituted the defective HIV-specific CD4þ T cells [De Paoli et al, 1997;Katlama et al, 2002;Hardy et al, 2004], and enabled them to produce more IL-2, which subsequently helped the proliferation of CD8þ T cells; and (4) IL-2 addition rescued HIV-specific CD8þ T cells from death after activation by specific peptide antigens [Zanussi et al, 1999;Marchetti et al, 2004]. In a previous study, it was clearly demonstrated that CD8þ T cells were extremely prone to activation induced apoptotic cell death in patients with HIV infection in comparison to HIV-uninfected controls [Meyaard et al, 1992].…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐2 reconstitutes defective human immunodeficiency virus (HIV), and cytomegalovirus (CMV) specific CD8+ T cell proliferation in HIV infection

Chen

Horton

et al. 2006

Journal of Medical Virology

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Recent studies indicate that a defective proliferative response of HIV-specific CD8+ T cells is associated with the lack of virologic control in chronic HIV infection in humans. The possible mechanisms that might be responsible for the reduced proliferative potential of HIV-specific CD8+ T cells and conditions conducive to the proliferation of CD8+ T cells were examined in 14 HIV-infected individuals and 7 HIV-uninfected controls using CFSE labeling and flow cytometry techniques, and analyzed data using 2 quantitative measurements: the percentages of proliferating CD8+ T cells (Tp), and the maximum number of cell divisions (Dm) after stimulation. It was found that CD8+ T cells from HIV-infected and -uninfected subjects proliferated equally well after polyclonal stimulation by phylohemagglutinin A (PHA); both groups reached a Tp of 92%-96% and a Dm of 5-8. However, in HIV-infected subjects, proliferation of HIV- and CMV-specific CD8+ T cells was significantly reduced compared to proliferation of CMV- specific CD8+ T cells from HIV-uninfected subjects. These defective proliferative responses of HIV- and CMV-specific CD8+ T cells were restored by the addition of IL-2 at the time of stimulation. These results may have implications for the design of immune modulation strategies in vivo.

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Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy

Abstract: Administration of interleukin-2 produces significant and sustained increase in CD4 cell counts in HAART-treated patients with persistent CD4 cell counts < 200 x 10(6) cells/l.

Cited by 67 publications

References 4 publications

Natural Regulatory T Cells and Persistent Viral Infection

Natural Regulatory T Cells and Persistent Viral Infection

IL-2 Regulates Perforin and Granzyme Gene Expression in CD8+ T Cells Independently of Its Effects on Survival and Proliferation

Interleukin‐2 reconstitutes defective human immunodeficiency virus (HIV), and cytomegalovirus (CMV) specific CD8+ T cell proliferation in HIV infection

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