Cell cooperation during in vivo anti-hapten antibody responses. V. Two synergistic Ly-1+23- helper T cells with distinctive specificities.

Experiments were carried out to determine the antigen specificity of two distinct helper T cells (Th) that act synergistically in adoptive secondary in vivo anti-hapten antibody responses. Both Th were present in anti-Ly-2 and-complement-treated spleen T cell populations, implying that both Th are Ly-1+,23-. Adding normal T cells or T cells primed to other carriers to specific carrier-primed T cells, using a variety of different protocols did not affect the helper activity of the specifically primed Th. Thus, both Th apparently are antigen-specific. Furthermore, Th primed with one carrier and boosted with that carrier plus hapten linked to a noncross-reactive carrier cannot help B cells. However, if a mixture of Ly-1 T cells from mice primed with two different carriers is transferred along with B cells, and the mice are boosted with hapten coupled to one of the two priming carriers, then giving the other carrier induces a significant increase in antibody production. Thus, only one of the two Th (Th1) requires a hapten-carrier bridge, while the other does not (Th2). However, both Th1 and Th2 are clearly antigen-specific and require stimulation with antigen to exert helper activity. Furthermore, these experiments strongly suggest that Th2 cannot express helper function in vivo in the absence of Th1. These findings, and the absence of Th2-like cells in agammaglobulinemic mice, were correlated with other studies in which two helper activities have been described. It was concluded that in vivo responses require an effective Th1-B cell interaction, whereas Th2, if stimulated with antigen, will augment certain portions of the antibody response, such as idiotype or allotype, and thus influence the quality of the antibody response directly.