Premium
CD4 + lymphocytes control gut epithelial apoptosis and mediate survival in sepsis
Author(s) -
Stromberg Paul E.,
Woolsey Cheryl A.,
Clark Andrew T.,
Clark Jessica A.,
Turnbull Isaiah R.,
McConnell Kevin W.,
Chang Katherine C.,
Chung Chun-Shiang,
Ayala Alfred,
Buchman Timothy G.,
Hotchkiss Richard S.,
Coopersmith Craig M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-119024
Subject(s) - apoptosis , biology , genetically modified mouse , immunology , sepsis , cd8 , adoptive cell transfer , transgene , intestinal epithelium , programmed cell death , homeostasis , microbiology and biotechnology , epithelium , cancer research , immune system , t cell , gene , genetics
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 inRag‐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 ofBcl‐2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut‐specific overexpression ofBcl‐2 fails to alter survival when the transgene is overexpressed inRag‐1mice. Further, adoptively transferring lymphocytes toRag‐1mice that simultaneously overexpress gut‐specificBcl‐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.—Stromberg, P.E., Wool‐sey, C.A., Clark, A.T., Clark, J.A., Turnbull, I.R., McConnell, K.W., Chang, K.C., Chung, C.‐S., Ayala, A., Buchman, T.G., Hotchkiss, R.S., Coopersmith, C.M. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis. FASEB J. 23, 1817–1825 (2009)