Demonstration of intratumoral infiltration of tumor-specific Lyt-1+2- T cells mediating delayed-type hypersensitivity response and in vivo protective immunity.
The present study demonstrates the intratumoral infiltration of lymphocytes mediating anti-tumor delayed-type-hypersensitivity (DTH) responses as well as in vivo protective immunity. The surface phenotype and tumor specificity of these effector lymphocytes were determined. X5563 tumor-infiltrating lymphoid cells were obtained from the tumor mass of syngeneic C3H/HeN mice 2 weeks after the intradermal inoculation of 10(6) viable X5563 tumor cells. These lymphoid cells consisted of Thy-1-positive (29-35%), surface immunoglobulin-positive (16-29%), large granule-positive (15-25%) and esterase-staining-positive (10-20%) cells. They were tested for anti-X5563 DTH responses by utilizing a local adoptive transfer system and for tumor-neutralizing activity in a Winn assay. The results indicate that X5563 tumor-infiltrating lymphoid cells exhibited appreciable anti-X5563 DTH responses and conveyed complete protection against the tumor. Treatment of these lymphoid cells with anti-Thy-1.2 or anti-Lyt antibodies plus complement revealed that the in vivo anti-tumor immune responses were mediated predominantly by a Lyt-1+2- T cell subset. Such Lyt-1+2- T cell-mediated immunity was tumor-specific, since X5563-infiltrating and syngeneic MH134 hepatoma-infiltrating cells exhibited DTH response and tumor-neutralizing activity selectively against the respective tumor cell types. Thus, these results indicate that tumor-specific in vivo-protective Lyt-1+2- T cells infiltrate into the tumor mass. The results are discussed in the context of 1) the interrelation of DTH responses and the tumor protection mediated by the Lyt-1+2- T cell subset and 2) possible cellular interactions between Lyt-1+2- T cells and co-existing nonspecific tumoricidal effector cells such as macrophages.
Tomita
S
S
Fujiwara
H
H
Yamane
Y
Y
Sano
S
S
Nakajima
H
H
Izumi
Y
Y
Arai
H
H
Kawanishi
Y
Y
Tsuchida
T
T
Hamaoka
T
T
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000276:immunology; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007109:Immunity; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen