PubMed · 8554118
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J F Emile, P Gaulard. 1996. CD56 lymphomas.. https://doi.org/10.1097/00000478-199602000-00018
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Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that has antiviral, antiproliferative, and immunoregulatory functions. There is increasing evidence that IFN-alpha has an important role in T-cell biology. We have analyzed the expression of IL-2Ralpha, c-myc, and pim-1 genes in anti-CD3-activated human T lymphocytes. The induction of these genes is associated with interleukin-2 (IL-2)-induced T-cell proliferation. Treatment of T lymphocytes with IFN-alpha, IL-2, IL-12, and IL-15 upregulated IL-2Ralpha, c-myc, and pim-1 gene expression. IFN-alpha also sensitized T cells to IL-2-induced proliferation, further suggesting that IFN-alpha may be involved in the regulation of T-cell mitogenesis. When we analyzed the nature of STAT proteins capable of binding to IL-2Ralpha, pim-1, and IRF-1 GAS elements after cytokine stimulation, we observed IFN-alpha-induced binding of STAT1, STAT3, and STAT4, but not STAT5 to all of these elements. Yet, IFN-alpha was able to activate binding of STAT5 to the high-affinity IFP53 GAS site. IFN-alpha enhanced tyrosine phosphorylation of STAT1, STAT3, STAT4, STAT5a, and STAT5b. IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the GAS elements. Taken together, our results suggest that IFN-alpha, IL-2, IL-12, and IL-15 have overlapping activities on human T cells. These findings thus emphasize the importance of IFN-alpha as a T-cell regulatory cytokine.
Dipeptidyl peptidase IV (DPIV, CD26) is known to be involved in the regulation of T lymphocyte and NK cell activation and proliferation in vitro. The molecular events of lymphocyte activation mediated by this ectopeptidase as well as their physiological ligands are only partly established. Particularly, the necessity of catalytic dipeptidase activity for the costimulatory function of this molecule has been controversial. Here we provide evidence for a direct involvement of DPIV/CD26 in early phosphorylation mechanisms which are known to be essential in the signal transduction cascade of human T lymphocytes. We have found that DPIV-specific inhibitors (Lys[Z(NO2)]-thiazolidide and -piperidide) are capable of inducing intracellular tyrosine phosphorylation in resting human T cells. On the other hand, both inhibitors decreased the PMA-induced tyrosine phosphorylation in human T cells in a dose-dependent manner. Furthermore, a linkage between CD26 and the tyrosine kinase p56(lck) was shown by inhibition of PMA-induced hyperphosphorylation of p56(lck) by means of DPIV-specific inhibitors. The data presented here suggest that the inhibition of DPIV enzymatic activity induces a inhibitory signal transmitted by tyrosine kinases which leads to a block in a PMA-induced downstream pathway. These results support the assumption that DPIV/CD26 is directly involved in early processes of T cell activation via its enzymatic activity.
Tenascin (TN) is an extracellular matrix protein which interferes with fibronectin (FN)-dependent cell attachment and activation as a natural antagonist to FN action. In this study, we examined the inhibitory effect of TN on T cell proliferation induced by immobilized anti-CD3 Ab combined with various costimulators in a serum-free condition. Consistent with previous studies, human T cell activation induced by anti-CD3 plus FN was completely inhibited by the addition of TN. Interestingly, TN could interfere with T cell proliferations costimulated by various very late activation antigen (VLA) integrin/ligand interactions such as VLA-4/FN, VLA-5/FN and VLA-6/laminin. Furthermore, lymphocyte function-associated antigen 1 (LFA-1)-, CD2- and CD28-costimulated T cell activation were also inhibited by TN, while TN could not affect the phorbol ester-stimulated T cell proliferation. Collectively, TN inhibits anti-CD3-induced T cell proliferation irrespectively of costimulatory molecules, suggesting that TN acts as a generally immunosuppressive extracellular matrix protein which potentially interferes with T cell receptor/CD3-mediated T cell activation.