The contribution of parasite-specific T cells to isotype restriction in Mesocestoides corti-infected mice.
Mice infected with the parasite Mesocestoides corti undergo a polyclonal antibody response that results in a hypergammaglobulinemia restricted to the IgM and IgG1 isotypes. It was found that a similar restriction to IgM and IgG1 could be observed in an in vitro lymphocyte culture system providing that the source of helper T cells was from infected animals. In order to characterize the helper T cells responsible for the restriction, helper T cell clones were generated. Attempts to obtain isotype-restricting helper T cell clones by using the intact, nonviable organism were unsuccessful in that these T cell clones promoted multiple antibody class expression. However, two types of CD4+ (cluster designation) T cell clones were generated by cultivation on the live organism that appeared relevant to the observed restriction. These T cells did not function as conventional carrier-specific helper T cells. Instead, they were shown to regulate T-dependent responses to 2,4-dinitrophenyl-keyhole limpet hemocyanin by 2,4-dinitrophenyl-specific B cells and keyhole limpet hemocyanin-primed T cells derived from uninfected mice. The helper phenotype of one regulatory clone enhanced the IgG1 response, whereas the other phenotype inhibited the production of the other non-IgM isotypes tested. It is concluded that the activities of these two prototype regulatory T cell clones may predominate in infected animals resulting in the IgM, IgG1 dominance of the antibody response.