TY - JOUR
T1 - Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation
AU - Janbazian, Loury
AU - Price, David A.
AU - Canderan, Glenda
AU - Filali-Mouhim, Abdelali
AU - Asher, Tedi E.
AU - Ambrozak, David R.
AU - Scheinberg, Phillip
AU - Boulassel, Mohamad Rachid
AU - Routy, Jean Pierre
AU - Koup, Richard A.
AU - Douek, Daniel C.
AU - Sekaly, Rafick Pierre
AU - Trautmann, Lydie
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1102610
DO - 10.4049/jimmunol.1102610
M3 - Article
C2 - 22210916
AN - SCOPUS:84856571506
SN - 0022-1767
VL - 188
SP - 1156
EP - 1167
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -