ROLE OF CD4-CELL ACTIVITY AGAINST IGG(2A)(B) IN IGH(A) MICE AND DURING INDUCTION OF IGG(2A)(B) ALLOTYPE SUPPRESSION IN IGH(A( AND CD8+ CELLSUBSETS DURING AMPLIFICATION OF NATURAL T)B) MICE/

Transfer into F1 Igh(a/b) mice of splenocytes from Igh(a) mice sensiti zed once against B cells from an Igh(b) congenic strain induces total, chronic, and IgG2a(b)(IgG2a of the Igh(b) haplotype)-specific allotyp e suppression in these recipients. We previously demonstrated that bot h the CD4+ and CD8+ T subsets were necessary for inducing suppression, but that CD8+ cells by themselves were sufficient for maintaining sup pression. We have studied the suppression induction capacity of differ ent mixtures of CD4+ and CD8+ subsets obtained by in vitro cytotoxic t reatment of T splenocytes from normal or sensitized Igh(a) mice, and w e have established that suppression induction requires the cooperation between CD4+ and CD8+ populations, both of which have to be IgG2a(b) specific. In addition, Igh(a) mice were sensitized in the absence of C D4+ or CD8+ cells by in vivo cytotoxic treatment performed before and after the sensitization in order to obtain an IgG2a(b)-specific CD4+ p opulation that has arisen in the absence of CD8+ cells, and vice versa . We found that only IgG2a(b)-specific CD4+ cells from anti-CD8-treate d mice (T' sens CD4+) had the ability to induce suppression in F1 Igh( a/b) hosts. Nevertheless, the real effector cells in this suppression model display the CD8+ phenotype, as in vivo cytotoxic anti-CD8 treatm ent of Igh(a/b) recipients of T'sens CD4+ abrogates the suppression in duction capacity. Taken together, these results show that T'sens CD4have an important capacity to recruit CD8+ anti-IgG2a(b) effector cell s from precursors that have been transferred with them into Igh(a/b) h osts. These precursors are actually derived from the T' sens CD4+ cell preparation, because we have recently demonstrated that suppression i s maintained by donor T cells throughout the recipient's life. CD4+ ce lls can have their anti-IgG2a(b) activity amplified only by means of t arget cells (i.e., B cells from Igh(b) congenic mice), whereas, in the absence of CD4+ cells, and despite the presence of target cells, CD8 cells seem unable to acquire this amplified activity.