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2016 ; 7
(10
): 10962-75
Nephropedia Template TP
gab.com Text
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English Wikipedia
Removal of regulatory T cells prevents secondary chronic infection but increases
the mortality of subsequent sub-acute infection in sepsis mice
#MMPMID26918357
Huo R
; Wang L
; Wang X
; Zhao Y
; Wang Y
; Zhao X
; Chang L
; Liu SL
; Tong D
; Zhang H
; Huang Y
Oncotarget
2016[Mar]; 7
(10
): 10962-75
PMID26918357
show ga
The immunosuppression following initial septic insult impairs resistance to
secondary infection. Modulation of lymphocytes population may help to develop an
effective therapeutic strategy. In this study, lipopolysaccharide (LPS)-induced
endotoxemia was employed as the initial septic insult. 24 hours later, mice
underwent cecal ligation and puncture to induce chronic or sub-acute peritonitis.
Potential usefulness of T regs deletion antibody (anti-CD25) in improving
LPS-induced immunosuppression and the survival of subsequent different infections
were evaluated. LPS injection induced lymphocyte loss and led to decreased IL-6,
TNF-? and IFN-?, and weakened bacteria clearance upon chronic peritonitis at 24 h
post-LPS, whereas reconstitution with lymphocytes reversed these changes.
LPS-induced T regs expansion contributed to T and NK cells decrease in number and
activity during sepsis. Depletion of T regs using anti-CD25 antibodies partly
prevented lymphocyte loss and increased the responses of T and NK cells to
subsequent stimulation, resulting in significantly increased bacterial clearance
and survival in a 2-hit model of chronic peritonitis, but which significantly
increased early mortality upon subsequently sub-acute infection. Yet, using lower
dosage of anti-CD25 antibodies to moderate down-regulate T regs levels could
partly improve bacterial clearance and survival in either chronic or sub-acute
infection. These results demonstrate that using anti-CD25 antibodies to deplete T
regs can ameliorate immunosuppression through increasing T cells and NK cells
responses in sepsis, which is beneficial for preventing subsequently chronic
infection, but will probably bring some deleterious effects for subsequent
sub-acute infection.