DEPENDENCY ON INTERCELLULAR-ADHESION MOLECULE RECOGNITION AND LOCAL INTERLEUKIN-2 PROVISION IN GENERATION OF AN IN-VIVO CD8(-CELL IMMUNE-RESPONSE TO MURINE MYELOID-LEUKEMIA() T)

The immune response to a murine myeloid leukemia (cell line C1498) was studied in vitro and in vivo, Natural killer (NK) cells and CD8(+) cy totoxic T lymphocytes (CTL) were shown to lyse C1498 in vitro through the binding of leukocyte function antigen-1 (LFA-1) on effecters and i ntercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on C1498 target c ells. However, the ability of nonimmunized mice to resist an in vivo c hallenge of a low dose (10(4)) of C1498 was NK-cell, but not T-cell de pendent. The failure of T cells to participate in the immune surveilla nce of a low leukemia burden appeared, in part, because of a lack of e xpansion of leukemia reactive CTL precursors (CTLp). Leukemia reactive CTLp frequency estimations in naive and leukemia bearing mice were no t significantly different (range, 1:20,600 to 1:74.000) in contrast to immunized mice (range, 1:1,400 to 1:4,400). Leukemia reactive CTLp co uld be expanded to a level that could apparently mediate in vivo immun e surveillance of 10(5) leukemia cells by injection of irradiated leuk emia cells intraperitoneally (IF) or subcutaneously (SC), but not intr avenously (IV), However, IV injection of 10(5) live leukemia cells eng ineered to secrete interleukin-2 (IL-2) resulted in systemic immunity mediated primarily by CD8(+) T cells. We conclude that NK cells can me diate immune surveillance of a low leukemia burden. CD8(+) CTL-mediate d immune surveillance can eliminate a higher leukemia burden than NK c ells, but requires T-cell help, which can be delivered by local IL-2. Both NK and CTL-mediated immune surveillance of C1498 murine myeloid l eukemia is dependent on recognition through the LFA-1:ICAM adhesion pa thway. (C) 1995 by The American Society of Hematology,