EFFECTS OF NON-MHC BACKGROUND GENES ON THE INDUCTION OF CD4-CELLS THAT PREVENT REJECTION OF A HIGHLY IMMUNOGENIC TUMOR, FBL-3( T)

This study showed that non-MHC genes common to (DBA/2 H-2d) and (DBA/1 H-2q) gave rise to suppressor T (T(s)) cells in the hybrid F1 mice be tween C57BL/6 (B6) strain in the anti-FBL-3 tumor responses. FBL-3, a Friend virus-induced tumor cell line of B6 mouse origin, is highly imm unogenic as shown by findings that syngeneic and hybrid F1 mice with s everal other inbred strains rejected up to 3 X 10(7) tumor cells inocu lated s.c. and generated potent CTL responses after mixed lymphocyte t umor cell culture. In contrast to these mice, (B6 x DBA/2) and (B6 x D BA/1)F1 mice did not reject the tumor as the tumor doses increased. Pr ogressive tumor growth in these F1 mice was blocked by an i.p. injecti on of cyclophosphamide (250 mg/kg) on day 10, but not on day 5, after tumor cell inoculation. Anti-CD4 (GK1.5) mAb exerted similar therapeut ic effects against tumor when given twice, between day 0 and 10, where as the additional injection of anti-CD8 mAb enhanced the tumor growth in mice that otherwise rejected the tumor. Thus, in the response of (B 6 x DBA/2)F1 mice to FBL-3 tumor cells, CD4+ T(s) seemed to down-regul ate the immunologically mediated regression of the tumor produced by C D8+ CTL. This was evidenced by limiting dilution culture analyses, whi ch showed that the frequency of an FBL-3-specific CTL precursor in the (B6 x DBA/2)F1 mice that rejected the tumor with anti-CD4 mAb was app roximately 7- to 9-fold higher than that in mice in which the tumor re gressed spontaneously. That more than one gene was involved in suppres sor T cell induction was shown by the tumor growth pattern in (B6 x DB A/2)F1 x B6 backcross and B6D2F2 mice.