Completely allogeneic spleen cells induced cytolytic neonatal tolerance to alloantigens, but failed to establish allo‐helper interactions with host T cells

Abstract

The injection of spleen cells from F1 mice into newborns from a parental strain results in the establishment of cytolytic tolerance to donor alloantigens and the development of a lupus‐like disease. This syndrome is the consequence of the recognition by alloreactive host CD4+ T cells of discordant major histocompatibility complex (MHC) class II antigens on semi‐allogeneic donor B cells. We have analysed whether completely allogeneic spleen cells are as able as semi‐allogeneic spleen cells to induce cytolytic tolerance to donor alloantigens and to co‐operate with alloreactive T cells for autoantibody production. BALB/c mice were injected at birth with Thy‐1‐depleted spleen cells from (C57BL/6 × BALB/c)F1 or C57BL/6 mice, either alone or in combination. Cytolytic tolerance was always induced, as manifested by persistence of chimerism and acceptance of skin allografts. However, only F1 semi‐allogeneic B cells were activated by alloreactive host T cells to produce anti‐DNA IgG antibody. The deficient co‐operation between BALB/c CD4+ T cells and completely allogeneic C57BL/6 B cells was confirmed after neonatal injection of (C57BL/6 × BALB/c)F1 (Igha) spleen cells together with C57BL/6 (Ighb) spleen cells. These mice developed anti‐DNA antibodies bearing only the Igha allotype. Similar results were observed in experiments of allogeneic interaction in vitro, in which BALB/c CD4+ T cells were cocultured with either (C57BL/6 × BALB/c)F1 or C57BL/6 B cells. The present results demonstrate that completely allogeneic spleen cells efficiently induced cytolytic unresponsiveness to donor alloantigens, but B cells contained in this spleen cell population were unable to establish allo‐helper interactions with alloreactive CD4+ T cells, suggesting that cytolytic and helper T‐cell interactions involved in alloreactivity may be different.