Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection

Lydie Trautmann*, Florentin Martial Mbitikon-Kobo, Jean Philippe Goulet, Yoav Peretz, Yu Shi, Julien Van Grevenynghe, Francesco Andrea Procopio, Mohamad Rachid Boulassel, Jean Pierre Routy, Nicolas Chomont, Elias K. Haddad, Rafick Pierre Sekaly

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةمراجعة النظراء

56 اقتباسات (Scopus)

ملخص

Immediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-γ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control.

اللغة الأصليةEnglish
الصفحات (من إلى)3466-3477
عدد الصفحات12
دوريةBlood
مستوى الصوت120
رقم الإصدار17
المعرِّفات الرقمية للأشياء
حالة النشرPublished - أكتوبر 25 2012
منشور خارجيًانعم

ASJC Scopus subject areas

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بصمة

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