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2018 ; 200
(9
): 3180-3187
Nephropedia Template TP
gab.com Text
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Altered Ratio of T Follicular Helper Cells to T Follicular Regulatory Cells
Correlates with Autoreactive Antibody Response in Simian Immunodeficiency
Virus-Infected Rhesus Macaques
#MMPMID29610141
Fan W
; Demers AJ
; Wan Y
; Li Q
J Immunol
2018[May]; 200
(9
): 3180-3187
PMID29610141
show ga
Individuals with chronic HIV-1 infection have an increased prevalence of
autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these
individuals are also autoreactive. However, the underlying mechanism(s) that
produce these autoreactive broadly neutralizing Abs remains largely unknown. The
highly regulated coordination among B cells, T follicular helper (T(FH)) cells,
and T follicular regulatory (T(FR)) cells in germinal centers (GCs) of peripheral
lymphatic tissues (LTs) is essential for defense against pathogens while also
restricting autoreactive responses. We hypothesized that an altered ratio of
T(FH)/T(FR) cells in the GC contributes to the increased prevalence of
autoreactive Abs in chronic HIV infection. We tested this hypothesis using a
rhesus macaque (RM) SIV model. We measured the frequency of T(FH) cells, T(FR)
cells, and GC B cells in LTs and anti-dsDNA and anti-phospholipid Abs from Indian
RMs, with and without SIV infection. We found that the frequency of anti-dsDNA
and anti-phospholipid Abs was much higher in chronically infected RMs (83.3%
[5/6] and 66.7% [4/6]) than in acutely infected RMs (33.3% [2/6] and 18.6% [1/6])
and uninfected RMs (0% [0/6] and 18.6% [1/6]). The increased ratio of T(FH)/T(FR)
cells in SIV infection correlated with anti-dsDNA and anti-phospholipid
autoreactive Ab levels, whereas the frequency of T(FR) cells alone did not
correlate with the levels of autoreactive Abs. Our results provide direct
evidence that the ratio of T(FH)/T(FR) cells in LTs is critical for regulating
autoreactive Ab production in chronic SIV infection and possibly, by extension,
in chronic HIV-1 infection.