Expression and function of LFA-1 on A-NK and T-LAK cells: role in tumor target killing and migration into tumor tissue.

ABSTRACT

To study the role of the adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) in lymphokine-activated natural killer (A-NK) and mitogen-stimulated lymphokine-activated T killer (T-LAK) cell function, we evaluated the correlation between LFA-1 expression, as well as conjugate formation and cytotoxicity. Furthermore, the role of LFA-1 in the extravascular phase of migration of A-NK and T-LAK cells into B16 tumor tissue in vivo was studied. We demonstrate an 8-fold increased LFA-1 expression on 4-day-old A-NK and T-LAK cells compared to unstimulated spleen cells. Moreover, we demonstrate that while LFA-1 expression on T-LAK cells was strictly correlated to conjugate formation and cytotoxic capacity, A-NK cells showed a less clear correlation between LFA-1 expression and these functions. Interestingly, anti-CD11a alone did not inhibit cytotoxicity, anti-CD18 alone did only inhibit cytotoxicity moderately (25%) whereas anti-CD11a and anti-CD18 in combination almost abrogated cytotoxicity against tumor targets P815 and YAC-1. Finally we demonstrate that pre-incubation of T-LAK cells with anti-bodies to CD11a and CD18 in combination inhibited their migration into the B16 tumors by more than 50-60%. In contrast, this pretreatment did not inhibit A-NK cell migration. This difference could not be explained by differences between A-NK and T-LAK cells with respect to LFA-1 expression, turnover of antibody-receptor complexes or complement-mediated lysis induced by the anti-LFA-1 antibodies. We conclude that T-LAK cell binding to and lysis of tumor target cells and migration into the intercellular space of tumors depend strongly on the expression of LFA-1. In contrast, LFA-1 expression of A-NK cells showed a less clear correlation to these functions.