Effects of non-MHC background genes on the induction of CD4+ T cells that prevent rejection of a highly immunogenic tumor, FBL-3

This study showed that non-MHC genes common to (DBA/2 H-2d) and (DBA/1 H-2q) gave rise to suppressor T (Ta) cells in the hybrid F1 mice between C57BL/6 (B6) strain in the antl-FBL-3 tumor responses. FBL-3, a Friend virus-induced tumor cell line of B6 mouse origin, is highly immunogenic as shown by findings that syngenelc and hybrid F1 mice with several other inbred strains rejected up to 3 × 107 tumor cells inoculated s.c. and generated potent CTL responses after mixed lymphocyte tumor cell culture. In contrast to these mice, (B6 × DBA/2) and (B6 × DBA/1)F1 mice did not reject the tumor as the tumor doses increased. Progressive tumor growth in these F1 mice was blocked by an I.p. Injection of cyclophosphamlde (250 mg/kg) on day 10, but not on day 5, after tumor cell inoculation. Antl-CD4 (GK1.5) mAb exerted similar therapeutic effects against tumor when given twice, between day 0 and 10, whereas the additional injection of antl-CD8 mAb enhanced the tumor growth in mice that otherwise rejected the tumor. Thus, In the response of (B6 × DBA/2)F, mice to FBL-3 tumor cells, CD4+ T8 seemed to down-regulate the immunologically mediated regression of the tumor produced by CD8+ CTL. This was evidenced by limiting dilution culture analyses, which showed that the frequency of an FBL-3-speclflc CTL precursor in the (B6 × DBA/2)F1 mice that rejected the tumor with antl-CD4 mAb was ∼7- to 9-fold higher than that in mice in which the tumor regressed spontaneously. That more than one gene was involved in suppressor T cell induction was shown by the tumor growth pattern in (B6 × DBA/2)F1 × B6 backcross and B6D2F2 mice.