BETA(2)-INTEGRIN DEPENDENT AGGREGATE FORMATION BETWEEN LB T-CELL LYMPHOMA AND SPLEEN-CELLS - ASSESSMENT OF CORRELATION WITH SPLEEN INVASIVENESS

LB is an aggressive T cell lymphoma which rapidly invades the spleen a nd lymph nodes of BALB/c mice after s.c. inoculation. We previously re ported that mAb directed against the beta2 chain of the leukocyte func tion-associated antigen-1 (LFA-1) adhesion molecule (CD18) blocked the invasion of LB cells into the spleen but not into the lymph nodes. Th e same antibody also blocked in vitro aggregate formation between norm al spleen cells and LB cells. However, aggregate formation between nor mal lymph node cells and LB cells was not detected, regardless of rati o. In an attempt to evaluate the association between aggregate formati on and tumor invasion of the lymphoid organs, we have now extended the study. Intravenous injection of anti-CD18 mAb, which blocked spleen i nvasion by LB cells, also blocked the formation of ex vivo aggregates, spontaneously generated in spleen, but not in lymph node, cell suspen sions of BALB/c mice s.c. inoculated with LB cells. In contrast, mAbs unable to block spleen invasion were ineffective inhibitors of both in vitro and ex vivo aggregate formation between spleen and LB cells. Sp leens of nude mice that did not provide a supportive environment for l ymphoma invasion, were also deficient in target cells forming aggregat es with LB cells. In line with this observation, enriched T cells form ed more aggregates with LB cells than did enriched non-T cells, indica ting the lymphoma's preferential binding to splenic T cells. Aggregate -borne LB cells and LB cells which were not included in aggregates, in vaded the spleen and the lymph nodes to the same extent. However, non- aggregated LB cells acquired the ability to form aggregates after 1 we ek of in vitro cultivation, suggesting that this capacity may also be acquired in vivo. Anti-CD44 mAb, in distinct contrast to anti-CD18 mAb , blocked LB cell invasion of the lymph node, but not of the spleen. H owever, when anti-CD44 mAb was co-injected with anti-CD18 mAb it antag onized the blocking effect of anti-CD18 mAb on spleen invasion and for mation of ex vivo splenic aggregates. The interpretation of these resu lts in conjunction with the association between splenic aggregate form ation and spleen invasion by LB cells is discussed.