Characterization of autoreactive helper T cells in a murine model of autoimmune haemolytic disease

Repeated immunization of mice with rat red blood cells (RRBC) results in the production of both erythrocyte autoantibodies and anti-RRBC antibodies. 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 here that autoreactive Th cells can be recovered from RRBC-immunized mice. The Th cells proliferate in vitro whether stimulated by self or rat 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 response is evident when mouse erythrocytes are used as the antigen. From cytotoxic depletion of T-cell subsets, the phenotype of the proliferating 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 to be involved in the experimental induction of autoimmune haemolytic disease in mice.