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Fibroblasts prevent apoptosis of IL‐2‐deprived T cells without inducing proliferation: a selective effect on Bcl‐x L expression
Author(s) -
GOMBERT W.,
BORTHWICK N. J.,
WALLACE D. L.,
HYDE H.,
BOFILL M.,
PILLING D.,
BEVERLEY P. C. L.,
JANOSSY G.,
SALMON M.,
AKBAR A. N.
Publication year - 1996
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.1365-2567.1996.d01-759.x
Subject(s) - stromal cell , apoptosis , biology , fibroblast , microbiology and biotechnology , cytokine , cell culture , cancer research , immunology , biochemistry , genetics
The apoptosis of human cytokine‐deprived activated T cells can be prevented by a soluble mediator secreted by fibroblasts, epithelial and endothelial cells, and this rescue occurs with fibroblasts from different species. Fractionation of WI38 fibroblast‐conditioned medium indicated that the survival‐promoting agent(s) were >30 000 MW. The continuous presence of the survival factor was required for prevention of apoptosis, which did not involve the induction of proliferation. Nevertheless, the co‐cultured T cells remained in a primed state. The expression of the apoptosis‐inducing proteins Bax and CD95 (Fas/Apo‐1) was either unchanged or slightly increased in fibroblast‐rescued T cells, suggesting that constraints on survival still existed after co‐culture. A fundamental observation in the present study was that although Bcl‐2 was reduced, the levels of Bcl‐x L was maintained in cytokine‐deprived T cells by fibroblast co‐culture. This suggests that fibroblasts and/or other stromal cells may promote activated T‐cell survival by a selective effect on Bcl‐x L expression, which is consistent with histological examination of activated T cells within lymphoid tissue in vivo . The rescued T cells could be re‐activated by CD3 antibody, but only in the presence of CD28 co‐stimulation, which induced both Bcl‐2 and Bcl‐x L expression and also proliferation. Thus, survival signals from stromal cells in tissue microenvironments may enable activated T‐cell persistence in a primed but quiescent state, and our data suggest that the regulation of Bcl‐x L expression may be central in this process. The further characterization of this process is essential to clarify how signals from stromal cells can influence the resolution and/or chronicity of immune responses in different tissues in vivo .