Extracellular matrix components of the mouse thymic microenvironment. II. In vitro modulation of basement membrane proteins by interferon-gamma: relationship with thymic epithelial cell proliferation.

We studied the effects of recombinant interferon-gamma (IFN-gamma) on some aspects of the physiology of two murine thymic epithelial cell (TEC) lines. Besides the expected induction of MHC class II antigens, this lymphokine was able to modulate the extracellular matrix (ECM) expression by growing TEC, as well as modulate their adhesion and proliferation patterns. As regards the influence of rIFN-gamma on ECM expression, we observed that when applied in very low doses, it promoted an increase in the amounts of basement membrane proteins, mainly fibronectin. In contrast, relatively high doses of this lymphokine (10(1) to 10(2) IU/ml) induced the opposite effect. Interestingly, both the stimulatory and the blocking effects of IFN-gamma on ECM expression were paralleled by equivalent modulation of cell proliferation, in both mouse and rat TEC lines. It should be pointed out that all these effects could be significantly abrogated by an anti-IFN-gamma monoclonal antibody. Searching for a putative mechanism that could be involved in the modulation of TEC proliferation by IFN-gamma, we observed a clear-cut positive correlation between cell adhesion and proliferation of TEC growing onto ECM-containing substrata produced following IFN-gamma treatment. The bulk of the data presented herein suggests that IFN-gamma may play a relevant role in TEC physiology and ontogeny, not only by inducing MHC class II antigen expression but also by regulating TEC growth via the control of extracellular matrix production by these cells.