CHARACTERIZATION OF HOST CD4-LYMPHOCYTES IN MICE NEONATALLY TOLERIZEDTO ALLOANTIGENS( T)

BALB/c mice injected at birth with semi-allogeneic F1 spleen cells bec ome tolerant to alloantigens as shown by their CTL unresponsiveness to the corresponding alloantigen and the persistence of donor F1 cells i nto the BALB/c host. Moreover, these mice develop a transient systemic lupus erythematosis-like autoimmune syndrome characterized by splenom egaly, glomerulonephritis, thrombocytopenia and abnormal serological f indings, such as several autoantibodies and IgG1 hypergammaglobulinemi a. Recent studies done in our laboratory have shown that donor F1 B ce lls persisting in the host are responsible for the production of autoa ntibodies and must be activated in vivo by the host CD4+ T lymphocytes in a MHC class II-restricted fashion. In the present work, we have fo cused our attention on the ability of splenic CD4+ T cells recovered a t different periods from BALB/c mice injected at birth with (CBA/Ca x BALB.Igh(b)) F1 spleen cells to interact with and activate F1 semi-all ogeneic spleen cells in vitro. We show that (i) only CD4+ T cells from 2- and 3-week-old tolerant BALB/c mice preferentially produce IL-4 an d IL-5 in response to a F1 semi-allogeneic in vitro stimulation, (ii) CD4+ T cells purified from 3-week-old tolerant BALB/c mice are able to induce in vitro IgG and IgM production by F1 B cells. Taken together, these results strongly suggest that host CD4+ T cells, belonging to t he TH2 subset progressively lose their reactivity towards the F1 semi- allogeneic persistent B cells, reaching a state of unresponsiveness th at correlates with the disappearance of serum autoantibodies and autoi mmune pathology.