CD4(-CELLS DETERMINE THE ABILITY OF SPLEEN-CELLS FROM F1-HYBRID MICE TO INDUCE NEONATAL TOLERANCE TO ALLOANTIGENS AND AUTOIMMUNITY IN PARENTAL MICE() T)

Spleen cells from F-1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding allo antigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomeru lonephritis. Previous reports indicated that the depletion of F-1 dono r T cells, shortly prior the injection into parental mice, does not in terfere with any of these events. Here, we have explored whether the c ontinuous absence of T cells in F-1 mice influences the ability of the ir spleen cells to induce neonatal tolerance to alloantigens and the a ssociated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c x C57BL/6) F-1 hybrid (CB6F(1)) nu/nu mice or from euthymic CB6F(1) mice depleted from birth of CD4(+) T cells, b ut not of CD8(+) T cells, are unable to induce neonatal tolerance to a lloantigens and autoimmune manifestations. By contrast, the partial re constitution of T cells in CB6F(1) nu/nu mice, after the neonatal graf t of a syngeneic thymus, restored the capacity of spleen cells from th ese mice to induce tolerance and autoimmunity when injected into newbo rn BALB/c mice. These results demonstrate that the functional defect o f spleen cells from athymic CB6F(1) nu/nu mice to induce neonatal tole rance to alloantigens is directly related to the long-term absence of mature CD4(+) T cells. Interestingly, a new increase in the titers of anti-DNA Ab was observed when spleen cells from athymic CB6F(1) nn/nu mice were injected into adult BALB/c mice that had been tolerized at b irth with normal CB6F(1) spleen cells. This finding indicates that B c ells from CB6F(1) nu/nu mice recover their capacity to interact with a lloreactive Th2 cells when they are placed into mice having functional CD4(+) T cells. These data indicate that the continuous absence of CD 4(+) T cells causes a reversible functional defect in Fl spleen cells that determines their inability to induce neonatal tolerance and autoi mmunity.