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.