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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+Immunol
2016 ; 197
(5
): 1832-42
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Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues
during Chronic Simian Immunodeficiency Virus Infection Defines Functionally
Distinct Germinal Center Tfh Cells
#MMPMID27481845
Velu V
; Mylvaganam GH
; Gangadhara S
; Hong JJ
; Iyer SS
; Gumber S
; Ibegbu CC
; Villinger F
; Amara RR
J Immunol
2016[Sep]; 197
(5
): 1832-42
PMID27481845
show ga
Chronic HIV infection is associated with accumulation of germinal center (GC) T
follicular helper (Tfh) cells in the lymphoid tissue. The GC Tfh cells can be
heterogeneous based on the expression of chemokine receptors associated with T
helper lineages, such as CXCR3 (Th1), CCR4 (Th2), and CCR6 (Th17). However, the
heterogeneous nature of GC Tfh cells in the lymphoid tissue and its association
with viral persistence and Ab production during chronic SIV/HIV infection are not
known. To address this, we characterized the expression of CXCR3, CCR4, and CCR6
on GC Tfh cells in lymph nodes following SIVmac251 infection in rhesus macaques.
In SIV-naive rhesus macaques, only a small fraction of GC Tfh cells expressed
CXCR3, CCR4, and CCR6. However, during chronic SIV infection, the majority of GC
Tfh cells expressed CXCR3, whereas the proportion of CCR4(+) cells did not
change, and CCR6(+) cells decreased. CXCR3(+), but not CXCR3(-), GC Tfh cells
produced IFN-? (Th1 cytokine) and IL-21 (Tfh cytokine), whereas both subsets
expressed CD40L following stimulation. Immunohistochemistry analysis demonstrated
an accumulation of CD4(+)IFN-?(+) T cells within the hyperplastic follicles
during chronic SIV infection. CXCR3(+) GC Tfh cells also expressed higher levels
of ICOS, CCR5, and ?4?7 and contained more copies of SIV DNA compared with
CXCR3(-) GC Tfh cells. However, CXCR3(+) and CXCR3(-) GC Tfh cells delivered help
to B cells in vitro for production of IgG. These data demonstrate that chronic
SIV infection promotes expansion of Th1-biased GC Tfh cells, which are
phenotypically and functionally distinct from conventional GC Tfh cells and
contribute to hypergammaglobulinemia and viral reservoirs.