Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation

Loury Janbazian, David A. Price, Glenda Canderan, Abdelali Filali-Mouhim, Tedi E. Asher, David R. Ambrozak, Phillip Scheinberg, Mohamad Rachid Boulassel, Jean Pierre Routy, Richard A. Koup, Daniel C. Douek, Rafick Pierre Sekaly, Lydie Trautmann*

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةArticleمراجعة النظراء

34 اقتباسات (Scopus)

ملخص

Persistent exposure to cognate Ag leads to the functional impairment and exhaustion of HIV-specific CD8 T cells. Ag withdrawal, attributable either to antiretroviral treatment or the emergence of epitope escape mutations, causes HIV-specific CD8 T cell responses to wane over time. However, this process does not continue to extinction, and residual CD8 T cells likely play an important role in the control of HIV replication. In this study, we conducted a longitudinal analysis of clonality, phenotype, and function to define the characteristics of HIV-specific CD8 T cell populations that persist under conditions of limited antigenic stimulation. Ag decay was associated with dynamic changes in the TCR repertoire, increased expression of CD45RA and CD127, decreased expression of programmed death-1, and the emergence of polyfunctional HIV-specific CD8 T cells. High-definition analysis of individual clonotypes revealed that the Ag loss-induced gain of function within HIV-specific CD8 T cell populations could be attributed to two nonexclusive mechanisms: 1) functional improvement of persisting clonotypes; and 2) recruitment of particular clonotypes endowed with superior functional capabilities.

اللغة الأصليةEnglish
الصفحات (من إلى)1156-1167
عدد الصفحات12
دوريةJournal of Immunology
مستوى الصوت188
رقم الإصدار3
المعرِّفات الرقمية للأشياء
حالة النشرPublished - فبراير 1 2012
منشور خارجيًانعم

ASJC Scopus subject areas

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  • ???subjectarea.asjc.2400.2403???

بصمة

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