Correlations of in vivo growth of CTL-susceptible and -resistant variant tumor cell lines in CTL-responder AKR.H-2b:Fv-1b and -nonresponder AKR.H-2b mice.

Spontaneously occurring lymphoma/leukemias in AKR and AKR.H-2b mice are characterized by their expression of the Gross cell surface antigen (GCSA) and their weak immunogenicity. Although of a responder H-2 type, AKR.H-2b mice could not raise cytolytic T lymphocytes (CTLs) against a syngeneic GCSA+ tumor (AKR.H-2bSL1). In contrast, AKR.H-2b:Fv-1b mice served as a source for "antiviral" CTLs specific for GCSA+ tumors such as AKR.H-2bSL1, but not for CTLs against the cl.18-5 variant tumor, an antiviral CTL-resistant subclone derived from AKR.H-2bSL1. In the present study in vivo tumor challenge experiments demonstrated that both the ability of the recipient strain to raise CTLs and the sensitivity of the tumor to the CTLs were critical factors which determine tumor growth and recipient mortality. Furthermore, the ability to raise protective immunity against AKR.H-2bSL1 and cl.18-5 tumor challenge by preimmunization was investigated. It was not possible to raise protective immunity in CTL-nonresponder AKR.H-2b mice. In the case of AKR.H-2b:Fv-1b mice, immunization with allogeneic GCSA+ E male G2 tumor cells leads to complete protective immunity--not only against parental AKR.H-2bSL1 but, somewhat surprisingly, also against cl.18-5 variant, tumor challenge. Consistent with these findings and at the same time with an in vivo role for antiviral CTL, however, CTLs directed to the E male G2, AKR.H-2bSL1, and cl.18-5 tumors could be generated from the spleens of mice which had rejected cl.18-5 tumor cells. Interestingly, immunization of AKR.H-2b:Fv-1b mice with syngeneic AKR.H-2bSL1 tumor cells failed to raise any protective immunity. Thus, the data suggested that the concurrent recognition of allogeneic components with tumor-associated transplantation antigens (TATA) might be important in the induction of sufficient protective immunity against syngeneic GCSA+ tumors. Finally, the possible relationship of TATA and retroviral antigens, such as gp70 and p30 or as defined by CTL clones, is discussed.