Hybrid resistance to EL-4 lymphoma cells. I. Characterization of natural killer cells that lyse EL-4 cells and their distinction from marrow-dependent natural killer cells.

Abstract

Natural killer (NK) cells from non-immunized mice capable of lysing EL-4 (C57BL/6 strain H-2b) tissue culture-adapted lymphoma cells were analyzed and compared with NK cells which lyse YAC-1 (A-strain, H-2a) lymphoma cells A correlation was seen in the ability of inbred and B6D2F1 mice to reject C57BL/6 (B6) bone marrow grafts and the ability of their spleen cells to lyse EL-4 cells in vitro. Hybrid or hemopoietic histocompatibility antigens [Ag] (Hh-1b) relevant in the rejection of B6 stem cells may be the relevant target structures for the anti-EL-4 NK cells. Certain features of these NK cells are similar to the NK cells reactive against YAC-1 cells. Both types of NK cells are present in athymic nude mice, are not affected by treatment with anti-immunoglobulin plus complement and are not depleted by techniques that remove macrophages. NK activity against both target is stimulated 3 d [days] after injection of Corynebacterium parvum [Propionibacterium acnes] and 24 h after challenge with poly(I:C). Hydrocortisone acetate and cyclophosphamide lead to reduction of NK activity 2-3 d after administration. The anti-YAC and anti-EL-4 NK reactivities differed in several important respects. Treatment of mice with 89Sr, the bone-seeking isotope, to deplete marrow-dependent cells, depleted the anti-YAC-1 but not anti-EL-4 cell functions. Anti-EL-4 NK cells were unaffected by silica particles in vivo or in vitro; the NK cells reactive to EL-4 cells matured functionally much earlier in life (5 d of age) and the function did not decline with age. Irradiated mice reconstituted with syngeneic marrow or spleen cells developed functional NK cells against EL-4 targets before they developed anti-YAC-1 NK cells in their spleen. Anti-EL-4 NK cells that express hybrid resistance in vitro appear to differ from anti-YAC-1 NK cells and do not require an intact marrow microenvironment for functional differentiation. Despite differences in the NK-cell types involved in the lysis of YAC-1 and EL-4 cells, these 2 tumor cells share certain common determinants. This was ascertained by cold competition and by utilization of YAC-1 and EL-4 cell monolayers as immunoadsorbents. Hh-1b is the common Ag present in EL-4 and YAC-1 cells; B6D2F1 anti-B6 (antiHh-1b) cytotoxic T [thymus-derived] lymphocytes lysed both the tumor cells. Hh-1b Ag may be recognized by both types of NK cells, but additional determinants probably must be present on YAC-1 cells. Two models of NK cell lysis compatible with the data are presented.