LYMPH-NODE (BUT NOT SPLEEN) INVASION BY MURINE LYMPHOMA IS BOTH CD44(-) AND HYALURONATE-DEPENDENT

Similar to activated T cells, LB T cell lymphoma expresses the CD44 ce ll surface Ag. In addition, the vast majority of LB cells also express the beta(2) (CD18) and alpha(L) (CD11a) chains of LFA-1 integrin. In view of the finding that anti-CD18 mAb blocked spleen, but not lymph n ode invasion by LB cells inoculated s.c. into BALB/c mice, we tested t he ability of anti-CD44 mAb (1M 7.8.1) to block the infiltration of LB cells into the lymph nodes. We found that, as opposed to anti-CD18 mA b, anti-CD44 mAb, as well as its F(ab'), or Fab fragment, prevented ly mph node infiltration but had no effect on spleen invasion. This concl usion was based on histologic examination and [H-3]thymidine incorpora tion into proliferating LB cells invading the lymphoid organs. Histolo gic analysis further demonstrated that LB cells invade the lymph node via the afferent lymphatics. The surface expression of CD44 molecules on LB cells was enhanced after PMA activation. PMA activation also ena bled in vitro binding of the lymphoma to hyaluronic acid (HA), a known ligand of CD44. Because anti-CD44 mAb, its F(ab'), or Fab fragment, a nd hyaluronidase blocked this binding, we also tested the ability of t he enzyme to inhibit lymph node invasion by LB cells. We established t hrough histologic examination and [H-3]thymidine incorporation that hy aluronidase protected the lymph node, but not the spleen, from invasio n by the lymphoma.