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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Virol
2014 ; 88
(20
): 11861-71
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
High eomesodermin expression among CD57+ CD8+ T cells identifies a CD8+ T cell
subset associated with viral control during chronic human immunodeficiency virus
infection
#MMPMID25100841
Simonetta F
; Hua S
; Lécuroux C
; Gérard S
; Boufassa F
; Sáez-Cirión A
; Pancino G
; Goujard C
; Lambotte O
; Venet A
; Bourgeois C
J Virol
2014[Oct]; 88
(20
): 11861-71
PMID25100841
show ga
During HIV infection, increased CD57 expression among CD8(+) T cells has been
associated with immune senescence and defective immune responses. Interestingly,
CD57-expressing CD8(+) T cells exhibit a dual profile, being simultaneously
highly cytotoxic (terminally differentiated effectors) and poorly proliferative
(replicative senescent). Recent publications point toward a positive role of
CD57-expressing CD8(+) T cell subsets, presumably due to their high cytolytic
activity. We further investigated the phenotype of CD57-expressing CD8(+) T cells
in healthy donors and during HIV infection combining CD57 expression to
Eomesodermin (EOMES), a T box transcription factor which determines, coordinately
with T-bet, effector and memory CD8(+) T cell differentiation. We defined in
healthy donors two functionally distinct CD57-expressing CD8(+) T cell subsets
exhibiting different levels of EOMES expression: EOMES(hi) CD57(+) and EOMES(int)
CD57(+) CD8(+) T cells. EOMES(hi) CD57(+) cells exhibited low cytotoxic activity
but preserved proliferative capacity and interleukin 7 (IL-7) receptor
expression, whereas EOMES(int) CD57(+) cells exhibited obvious cytotoxic
functions and a more terminally differentiated phenotype. We next performed a
similar analysis in different contexts of HIV infection: primary infected
patients, long-term viremic patients, aviremic patients treated with
antiretroviral therapy, and HIV controllers; we demonstrated a higher percentage
of CD57-expressing cells in all HIV-infected patients regardless of virological
status. When heterogeneity in EOMES expression among CD57 cells was taken into
account, we detected significantly higher proportions of EOMES(hi) CD57(+) cells
among HIV-specific and nonspecific CD8(+) T cells from HIV controllers than in
aviremic antiretroviral-treated patients and viremic patients. Importantly, such
a peculiar non-terminally differentiated EOMES(hi) CD57(+) phenotypic profile was
associated with viral control. Importance: This study demonstrates that
functional heterogeneity exists among CD57-expressing CD8 T cells, which include
both terminally differentiated, highly cytotoxic EOMES(int) CD57(+) CD8(+) T
cells and less differentiated EOMES(hi) CD57(+) CD8 T cells, which do not exhibit
immediate cytotoxic functions but present high proliferative capacity.
Interestingly, HIV controllers present a high proportion of EOMES(hi) CD57 cells
among CD57-expressing HIV-specific CD8 T cells compared to both long-term viremic
and aviremic antiretroviral therapy (ART)-treated patients, suggesting a
beneficial role for this cell subset in viral control.