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Increased inducible apoptosis in CD4 + T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin
Author(s) -
Alfred Ayala,
ChunShiang Chung,
Ying Xu,
Tracy A. Evans,
K. M. Redmond,
Irshad H. Chaudry
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00765.x
Subject(s) - fas ligand , splenocyte , biology , concanavalin a , cd8 , immunology , immune system , apoptosis , cytokine , lymphocyte , sepsis , endocrinology , medicine , microbiology and biotechnology , programmed cell death , in vitro , biochemistry
Recent studies suggest that increased lymphocyte apoptosis (A o ) detected in peripheral blood T cells from burn patients appears to contribute to decreased lymphocyte immunoresponsiveness. However, while it is known that sepsis induces a marked depression in the splenocyte immune response (i.e. decreased interleukin‐2, interferon‐γ production and proliferation) in response to the T‐cell mitogen concanavalin A (Con A), it is unknown whether this depression is associated with an increase in inducible A o and if so, which mediators control this process. To assess this, splenocytes were harvested from mice at 24 hr (a period associated with decreased Con A response) after the onset of polymicrobial sepsis [caecal ligation and puncture (CLP)] or sham‐CLP (Sham) and then stimulated with 2·5 μg Con A/ml (24 hr). Septic mouse splenocytes stimulated with Con A, while not showing a change in their phenotypic make‐up, did exhibit a marked increase in the percentage of splenocyte that were A o + which was associated with altered cytokine release. This appears to be due to an increase in the percentage of A o + cells in the CD4 + CD8 − population and was associated with enhanced Fas antigen expression as well as an increase in mRNA for the Fas–FasL gene family. To determine if the changes in A o are due to either endotoxin (a product of Gram‐negative bacteria seen in CLP mice) or the expression of Fas ligand (FasL; a mediator of activation‐induced lymphocyte A o ), a second set of studies examining Con A‐inducible A o was performed with splenocytes harvested from septic endotoxin‐tolerant C3H/HeJ and the FasL‐deficient C3H/HeJ‐ Fasl gld mice. The results show that increased splenocyte A o detected following CLP is due to a FasL‐mediated process and not to endotoxin. Thus the inadvertent up‐regulation of FasL‐mediated splenocyte A o may contribute to the depression of splenocyte immune responses seen during polymicrobial sepsis.