CD28 is not required for rejection of unmanipulated syngeneic and autologous tumors.
To gain a better understanding of the requirement of CD28 co-stimulation in different types of T cell-dependent tumor rejection responses, we performed a series of syngeneic and autologous tumor rejection experiments on CD28 knockout mice. In a preimmunization-challenge model, virally-induced ALC lymphoma and methylcholanthrene-induced MC57X fibrosarcoma transplants were rejected similarly by syngeneic CD28 knockout and immunocompetent controls. ALC-specific cytotoxic T lymphocytes (CTL) and MC57X-specific tumor necrosis factor (TNF) release were induced in CD28 knockouts, although at a reduced level in the latter case. Secondly, the spontaneous regression of Moloney murine sarcoma virus (MMSV)-induced primary tumors in the autologous hosts occurred equally in CD28 knockouts and in immunocompetent control mice. A comparable virus-specific CTL response was generated in both, as revealed in cytolytic assays against RBL-5 targets. Thirdly, the spontaneous rejection of the B7-transfected EL-4 lymphoma by immunocompetent hosts was abrogated in CD28 knockout mice, since more than 82% CD28 knockouts developed tumors after inoculation with B7-transfected EL-4 cells. Our results therefore show that CD28 co-stimulatory molecules are not required for the rejection of unmanipulated syngeneic tumors in hyperimmunized hosts and the regression of MMSV-induced sarcoma in autochthonous hosts.
Wen
T
T
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Kono
K
K
Shahinian
A
A
Kiessling
R
R
Mak
T W
TW
Klein
G
G
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D005354:Fibrosarcoma / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007114:Immunization; D016399:Lymphoma, T-Cell / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008980:Moloney murine sarcoma virus; D009368:Neoplasm Transplantation / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014182:Transplantation, Autologous; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018122:B7-1 Antigen; D018106:CD28 Antigens; D014409:Tumor Necrosis Factor-alpha