Capacity of CD8+ T cells to reject immunogenic variants of a spontaneous murine carcinoma: lack of non-specific (NK1.1+) effector mechanisms.
Class I MHC-expressing (Ia-) immunogenic (imm +) variants, which elicit a strong syngeneic host immune rejection response, can be isolated following 5-azacytidine treatment from the MHC-negative non-immunogenic (imm-) murine carcinoma cell line SP1 (10.1 subclone). In the present study, we have shown that CD4-depleted CD8+ T cells are both necessary and sufficient for the rejection process. Treatment of semi-syngeneic B6 X CBA F1 mice with anti-NK1.1 antibodies had no effect on the rejection of immunogenic variants, although the splenic NK (natural killer) activity of recipients was fully abrogated. Thus NK1.1+ effectors, which include most NK and LAK (lymphokine activated killer) cells, are most likely not involved in the rejection process. This finding was supported by a complete lack of NK susceptibility of SP1 cells in vitro, although variable killing by LAK and poly-I: C-induced killer cells was observed. To assess the role of NK1.1-LAK and other non-T killers (e.g. cytolytic macrophages) in vivo, we determined the specificity of the rejection process. We examined the ability of immune animals to reject a mixture of non-immunogenic parent tumour cells (or cells of an unrelated syngeneic tumour) and of the variant tumour cells used for the initial immunization. Growth of the parent tumour cells was unaffected while the same animals rejected the immunogenic tumour cells. Our findings support a primary role of tumour-specific CD8+ T cells in the rejection of imm+ variants with no detectable involvement of non-specific effector cells in the tumour destruction process.
Elliott
B E
BE
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Barron
A
A
Maxwell
L
L
Carlow
D A
DA
MacNaughton
S
S
Pross
H
H
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection; D007694:Killer Cells, Natural / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*