Fibroblasts prevent apoptosis of IL-2-deprived T cells without inducing proliferation: a selective effect on Bcl-XL expression. Academic Article uri icon


  • 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 W138 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 cell 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.

published proceedings

  • Immunology

author list (cited authors)

  • Gombert, W., Borthwick, N. J., Wallace, D. L., Hyde, H., Bofill, M., Pilling, D., ... Akbar, A. N.

citation count

  • 56

complete list of authors

  • Gombert, W||Borthwick, NJ||Wallace, DL||Hyde, H||Bofill, M||Pilling, D||Beverley, PC||Janossy, G||Salmon, M||Akbar, AN

publication date

  • November 1996