Fibroblasts prevent apoptosis of IL‐2‐deprived T cells without inducing proliferation: a selective effect on Bcl‐xL expression

• Published in: Immunology Vol. 89; no. 3; pp. 397 - 404
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01-11-1996
• Subjects: Apoptosis - immunology; bcl-X Protein; CD4-Positive T-Lymphocytes - immunology; Cell Culture Techniques; Cell Cycle - immunology; Cell Line; fas Receptor - metabolism; Fibroblasts - immunology; Humans; Immunologic Memory; Interleukin-2 - immunology; Leukocyte Common Antigens - metabolism; Lymphocyte Activation - immunology; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.1996.d01-759.x

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‐xL 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‐xL 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‐xL 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‐xL 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.