Faculty Bibliography

The expression of major histocompatibility complex (MHC) class II molecules in murine T cells has been controversial. We therefore reexamined the transcription, synthesis and surface expression of MHC class II determinants in rat T cells both in vivo and in vitro. In naive rats, a large proportion of small CD4+8+ and mature CD4+8-/CD4-8+ thymocytes was found to be MHC class II positive. At least some of the MHC class II molecules found on thymocytes were actively synthesized. The synthesis of MHC class II proteins was detected in peripheral T cells activated in vivo during induction of experimental allergic encephalomyelitis (EAE). A proportion of T cells from the inflammatory lesion of EAE exhibited MHC class II on the surface. A panel of helper T cell lines and clones was shown to synthesize MHC class II proteins. In a prototypic clone, a weak constitutive expression of MHC class II was observed. During activation, the rate of endogenous MHC class II synthesis increased and passive absorption of surface MHC class II from other cells occurred. Our data demonstrate the expression of MHC class II molecules in rat T cells in both the thymus and periphery. Since the primary function of MHC class II molecules is the presentation of peptide epitopes to T cells, these results call attention to the possible role of MHC class II molecules in T-T interactions during T cell maturation and activation.

Certain inflammatory cytokines and growth factors have been previously shown to interact with glycosaminoglycan moieties of the extracellular matrix (ECM). We have examined the association of the pleiotropic cytokine TNF-alpha with glycoprotein constituents of ECM. TNF-alpha interacted with fibronectin (FN) and laminin, and to a lesser degree with collagen. The major binding site for TNF-alpha on FN was localized to its 30-kDa N-terminal fragment (FN-N') with a Ki in the sub-nM range. The binding of 125I-labeled TNF-alpha to immobilized FN or FN-N' persisted for at least 24 h, and was specifically inhibited by antibodies to FN, mAb directed against the FN-N' domain, unlabeled TNF-alpha, and by the truncated forms of TNF-alpha receptors. Once bound to immobilized FN or FN-N', the cytokine could not be released by the soluble TNF-alpha-receptors, although it could be released by anti-TNF-alpha Ab. TNF-alpha was also found to interact with soluble FN, although with a lower affinity. Similar to the soluble cytokine, the FN-bound TNF-alpha appears to be functional; it augmented the beta 1-integrin-mediated adhesiveness of activated CD4+ human T cells to the glycoprotein. Hence, binding of TNF-alpha to immobilized FN, which modifies its functional accessibility to soluble TNF-alpha receptors, does not abolish but rather may locally restrict its activity. This study suggests that a major ECM glycoprotein can present, in a restricted manner, a functional adhesion-modulating cytokine to immune cells, and that ECM glycoproteins may regulate their intrinsic cell-adhesive properties by associating with cytokines.