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Unformatted text preview: HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype Asier Sa ´ez-Cirio ´ n † , Christine Lacabaratz ‡ , Olivier Lambotte ‡§ , Pierre Versmisse † , Alejandra Urrutia ‡ , Faroudy Boufassa ¶ , Franc ¸oise Barre ´-Sinoussi † , Jean-Franc ¸ois Delfraissy ‡§ , Martine Sinet ‡ , Gianfranco Pancino † i , and Alain Venet ‡,†† for the Agence Nationale de Recherches sur le Sida EP36 HIV Controllers Study Group † Unite ´ de Re ´gulation des Infections Re ´trovirales, Institut Pasteur, 75725 Paris, France; ‡ Unite ´ 802, Institut National de la Sante ´ et de la Recherche Me ´dicale, Faculte ´ de Me ´decine Paris XI, 94276 Le Kremlin-Bice ˆtre, France; and § Service de Me ´decine Interne et Maladies Infectieuses and ¶ Unite ´ 569, Institut National de la Sante ´ et de la Recherche Me ´dicale/Institut National des Etudes De ´mographiques, Ho ˆ pital Bice ˆtre, 94276 Le Kremlin-Bice ˆtre, France Edited by Dan R. Littman, New York University Medical Center, New York, NY, and approved February 27, 2007 (received for review December 18, 2006) Some rare HIV-1-infected individuals, referred to as HIV controllers (HIC), have persistently undetectable plasma viral load in the absence of therapy. This control of HIV-1 replication has been associated with a strong, multifunctional specific CD8 1 T cell response. However, no direct link between this immune response and the control of viremia has so far been provided. We investi- gated parameters of specific CD8 1 T cell response and in vitro susceptibility to HIV-1 infection in 11 HIC. We found high frequen- cies of HIV-specific CD8 1 T cells. Interestingly, these cells expressed the activation marker HLA-DR but not CD38. This unique pheno- type differentiates HIV-specific CD8 1 T cells from HIC and noncon- troller subjects and likely reflects a high potential to expand upon exposure to antigen and a capacity to exert effector functions. Accordingly, although CD4 1 T cells from HIC were fully susceptible to HIV-1 superinfection, their CD8 1 T cells effectively suppressed HIV-1 infection. Remarkably, this potent anti-HIV activity was observed without prior stimulation of CD8 1 T cells. This activity was not mediated by secreted inhibitory factors but was due to the elimination of infected CD4 1 T cells and was observed only with autologous CD4 1 T cells, indicating an HLA-restricted cytotoxic mechanism. This constitutive antiviral capacity of CD8 1 T cells could account for the control of viral replication in HIC. HIV suppression u CD8 1 T cells u HLA-DR u CD38 M ost untreated HIV-1-infected individuals have continuous viral replication and ultimately progress to AIDS. However, a rare subpopulation of HIV-infected patients spontaneously con- trol viral replication for long periods in the absence of treatment (1–5). These individuals, referred to here as HIV controllers (HIC), are characterized by undetectable plasma HIV-1 RNA. Some HICare characterized by undetectable plasma HIV-1 RNA....
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This note was uploaded on 11/01/2010 for the course A B taught by Professor C during the Spring '10 term at HKU.
- Spring '10