CHARACTERIZATION OF AUTOREACTIVE HELPER T-CELLS IN A MURINE MODEL OF AUTOIMMUNE HEMOLYTIC-DISEASE

Repeated immunization of mice with rat red blood cells (RRBC) results in the production of both erythrocyte autoantibodies and anti-RRBC ant ibodies. The manner in which erythrocyte self-tolerance is broken has been little studied. It has been assumed that help for autoreactive B cells is provided by Th cells specific for the foreign RRBC. We show h ere that autoreactive Th cells can be recovered from RRBC-immunized mi ce. The Th cells proliferate in vitro whether stimulated by self or ra t erythrocytes. Analysis of the specificity of the proliferating cells revealed extensive cross-reactivity for the two types of erythrocytes . It is therefore surprising that, in initial cultures, a slower respo nse is evident when mouse erythrocytes are used as the antigen. From c ytotoxic depletion of T-cell subsets, the phenotype of the proliferati ng cells was identified as Thy-1.2+, Lyt-1.1+, Lyt-2.1-, L3T4+. During in vitro stimulation of the T cells, growth factors characteristic of Th cells are secreted. Finally, we demonstrate that the responding T cells are able to help primary in vitro antibody responses to self and rat erythrocytes. We conclude that autoreactive Th cells are likely t o be involved in the experimental induction of autoimmune haemolytic d isease in mice.