B7-1 enhances natural killer cell-mediated cytotoxicity and inhibits tumor growth of a poorly immunogenic murine carcinoma.
The B7-1 molecule expressed on antigen presenting cells is an important costimulatory molecule for T cell activation. It has been demonstrated that murine B7-1 can enhance host immunity and lead to tumor rejection via its costimulatory function. Here, we investigate how transfection of B7-1 into line 1, a poorly immunogenic murine lung carcinoma, affects the generation and function of different immune effector cells. Line 1 cells expressing B7-1 form tumors that grow at a slower rate than the parental line 1. Our studies have shown that tumor infiltrating lymphocytes present within the B7-1 expressing tumors are primarily composed of nonspecific killer cells with no specific cytotoxic T cells present. To determine if increased nonspecific killer cells could inhibit the tumor growth of line 1 in the presence of B7-1, we examined the cytotoxicity of natural killer (NK) cells and lymphokine-activated killer (LAK) cells on the B7-1-transfected line 1 and the parental line 1. We found that B7-1 augments the NK- but not LAK-mediated killing against line 1 as measured in an in vitro 51Cr-release cytotoxicity assay. This enhancement could be blocked by CTLA-4 Ig. In vivo depletion of NK cells led to growth of the B7-1-transfected line 1 at the same rate as the parental line 1. These results suggest that in addition to its costimulatory role for T cell activation B7-1 could be an accessory molecule that intensifies NK-mediated cytotoxicity. This novel finding may provide a mechanism for the effect of B7-1 on tumors of low immunogenicity.
Yeh
K Y
KY
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Pulaski
B A
BA
Woods
M L
ML
McAdam
A J
AJ
Gaspari
A A
AA
Frelinger
J G
JG
Lord
E M
EM
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology*; D060908:CTLA-4 Antigen; D003602:Cytotoxicity, Immunologic; D018796:Immunoconjugates; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept