The CD44 variant isoforms CD44v6 and CD44v7 are expressed by distinct leukocyte subpopulations and exert non-overlapping functional activities

We have described recently that anti-CD44s, anti-cD44v6 and anti-CD44v7 int erfere with delayed-type hypersensitivity (DTH) reactions. Yet, TNBS-induce d colitis can be cured only by anti-CD44v7. To clarify the mechanisms under lying the divergent functional activities of CD44v6 and CD44v7 we explored their contribution to lymphocyte activation in vivo and in vitro. CD44v6 an d CD44v7 are distinctly expressed on subpopulations of activated lymphocyte s. Expression of CD44v6 is mainly restricted to T cell blasts. CD44v7 has b een detected on CD4(+) cells, B cells and monocytes. Mitogenic and antigeni c stimulation of lymphocytes in vitro was impaired in the presence of anti- CD44v6 and anti-CD44v7. Accordingly, anti-CD44v6 and anti-CD44v7 mitigated the DTH reaction in 2,4-dlnitro-1-fluorobenzene-sensitized and challenged m ice. However, the seemingly similar effects of CD44v6- and CD44v7-specific antibodies resulted from different activities. Anti-CD44v6 treatment led to a down-regulation of IL-2 and IFN-gamma production predominantly by CD8(+) cells. In anti-CD44v7-treated mice expression of IL-12 was decreased. Elev ated levels of IL-10 accompanied this reduction. The latter resulted from a n anti-CD44v7-mediated blockade of interactions between CD4+ cells and mono cytes as well as an active triggering of B cells. Thus, anti-CD44v7 and ant icD44v7 interfere with lymphocyte activation at very specific points. CD44v 6 functions predominantly at the T cell level. CD44v7 influences production of proinflammatory cytokines by B cells as well as an interaction between CD4(+) cells and antigen-presenting cells. As CD44 isoforms do not differ i n their intracytoplasmatic tail, the distinct activities must result from e xpression on different leukocyte subsets and interactions with distinct lig ands.