Activated T lymphocytes regulate hyaluronan binding to monocyte CD44 via production of IL-2 and IFN-gamma

Interactions of the cell surface proteoglycan CD44 with the extracellular m atrix glycosaminoglycan hyaluronan (HA) are important during inflammatory i mmune responses. Our previous studies indicated that monocyte HA binding co uld be induced by TNF-alpha. Moreover, monocyte HA binding could be markedl y up-regulated by culturing PBMC with anti-CD3 (TCR complex) mAbs. The pres ent study was undertaken to identify soluble factors and/or cell surface mo lecules of activated T lymphocytes that might regulate HA binding to monocy tes, Abs to IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-10, IL-15, GM-CSF, IFN-ga mma and TNF-alpha were tested for their effects on anti-CD3 mAb-, Con A-, a nd PMA/ionomycin-mediated monocyte HA binding in PBMC cultures. Anti-TNF-al pha, anti-IL-2, and anti-IFN-gamma Abs, when added together to PBMC culture s, completely blocked Con A- and partially blocked anti-CD3- and PMA/ionomy cin-induced monocyte HA binding. Furthermore, when added together to PBMC c ultures, IL-2 and TNF-alpha induced high levels of monocyte HA binding. Lik ewise, IFN-gamma augmented TNF-alpha -induced monocyte HA binding. To inves tigate the role of T cell-monocyte direct contact in induction of monocyte HA binding, we studied PMA/ionomycin-activated, paraformaldehyde-fixed CD4( +) T cells in these assays. Fixed, PMA/ionomycin-activated CD4(+) T lymphoc ytes induced monocyte HA binding, but direct T cell-monocyte contact was no t required. Moreover, anti-IFN-gamma and anti-TNF-alpha Abs blocked fixed P MA/ ionomycin-activated CD4(+) T cell-induced monocyte HA binding. Taken to gether, these studies indicate roles for soluble T lymphocyte-derived facto r(s), such as IL-2 and IFN-gamma, and a role for monocyte-derived TNF-alpha in Con A-, TCR complex-, and PMA/ionomycin-induced HA binding to monocyte CD44.