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CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.
- Source :
-
FASEB Journal . Jun2009, Vol. 23 Issue 6, p1817-1825. 9p. 2 Diagrams, 4 Graphs. - Publication Year :
- 2009
-
Abstract
- Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1-/- and wild-type (WT) mice. However, Rag-1-/- animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1-/- mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4+ but not CD8+, γδ, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1-/- mice. Further, adoptively transferring lymphocytes to Rag-1-/- mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4+ lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 23
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 41579271
- Full Text :
- https://doi.org/10.1096/fj.08-119024