B7-1 Enhances Natural Killer Cell-Mediated Cytotoxicity and Inhibits Tumor Growth of a Poorly Immunogenic Murine Carcinoma

Autor: Melody L. Woods, Beth A. Pulaski, Edith M. Lord, John G. Frelinger, Alexander J. McAdam, Anthony A. Gaspari, Kun Yun Yeh
Rok vydání: 1995
Předmět:
Zdroj: Cellular Immunology. 165:217-224
ISSN: 0008-8749
DOI: 10.1006/cimm.1995.1208
Popis: 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 51 Cr-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.
Databáze: OpenAIRE
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