Induction of Moloney murine sarcoma virus tolerance in adult mice by anti-CD4 monoclonal antibody treatment.
The role of CD4+ cells in the immune response to Moloney murine sarcoma/leukemia virus complex was studied in adult mice undergoing long-term CD4+ cell functional depletion by treatment with anti-CD4 H129.19 monoclonal antibody (immunoglobulin G2a, kappa). Adult mice given injections of Moloney murine sarcoma/leukemia virus complex 1 day or 2 wk after monoclonal antibody treatment died with progressing sarcomas at the inoculation site; mice challenged 4 wk after such treatment, when CD4+ cells recovered their functional activity, behaved like conventional mice; i.e., they spontaneously regressed the virus-induced sarcomas. Mice with progressing tumors did not generate virus-specific cytotoxic T-lymphocytes, despite a normal cytotoxic T-lymphocyte response to unrelated antigens, and they became virus carriers as demonstrated by Moloney murine leukemia virus antigen expression on their lymphoid cells a few days after virus injection. Moreover, the observed T-lymphocyte unresponsiveness was not due to the activity of specific suppressor T-cells. The findings indicate that the transient functional depletion of CD4+ cells at the time of virus administration provides appropriate environmental conditions for the spread of virus and facilitates tolerance induction.
Biasi
G
G
Institute of Oncology, CIRC, University of Padua, Italy.
Mazzocchi
M
M
Facchinetti
A
A
Panozzo
M
M
Zanovello
P
P
Collavo
D
D
Chieco-Bianchi
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000956:Antigens, Viral / Q000032:analysis; D015704:CD4 Antigens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008980:Moloney murine sarcoma virus / Q000276:immunology*; D009053:Sarcoma Viruses, Murine / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D015704:CD4 Antigens