FUNCTIONAL-ACTIVITY OF MURINE CD44 VARIANT ISOFORMS IN ALLERGIC AND DELAYED-TYPE HYPERSENSITIVITY

There is ample evidence that the family of CD44 glycoproteins is invol ved in homing, maturation and activation of lymphocytes. Furthermore, recent evidence suggests that CD44 splice variants are particularly in volved in the process of lymphocyte activation whereby it was hypothes ized that different isoforms may fulfill distinct functions. We here a ddressed the question of CD44v6 and CD44v7 being involved in T(H)1 and T(H)2 reactions using as model systems for T(H)1 activation a TNBS-in duced colitis and a DNFB-induced DTH reaction and for T(H)2 activation a FITC-induced allergic dermatitis. With the exception of a small sub population of lymphocytes in Peyer's patches, expression of neither CD 44v6 nor CD44v7 was noted in the absence of an antigenic stimulus. Bot h CD44 variant exons are transiently detected on T lymphocytes during mounting of an immune response. In vitro studies revealed that antibod ies against both CD44v6 and CD44v7 inhibited lymphocyte proliferation and cytokine production. Based on these findings the efficiency of ant i-CD44v6 and anti-CD44v7 treatment was evaluated in vivo in T(H)1 and T(H)2 dependent autoimmune and DTH reactions, Anti-CD44v7 completely a brogated development of a death promoting colitis and anti-CD44v6 as w ell as anti-CD44v7 significantly mitigated the DNFB-induced, T(H)1-med iated DTH reactions, while only anti-CD44v7 interfered with a FITC-ind uced, T(H)2-mediated allergic contact dermatitis. The in vitro analysi s of cytokine producing cells supported the assumption. In conclusion, it could be demonstrated that CD44v6 and CD44v7 are differentially in volved in T(H)1 and T(H)2 activation and, most importantly, a T(H)1-me diated autoimmune disease could be prevented by local application of a nti-CD44v7. (C) 1997 Elsevier Science B.V.