Characterization of an unusual cell type (CD4+ CD3-) expanded by helminth infection and related to the parasite stress response.

Mice infected with the parasite Mesocestoides corti develop hypergammaglobulinemia, hepatomegaly, and splenomegaly. The immune response to M. corti infection is directed, in part, at molecules secreted by the organism. Two of these molecules have been shown to be hsp70 and hsp60 homologues. In this study it was found that incubation of splenocytes from infected animals with M. corti-secreted molecules or the isolated M. corti hsp70 results in the expansion of an unusual cell type with the morphology of large granular lymphocytes. The cell lines express Thy-1, CD4 (low), and CD45RB but lack TCR alpha beta, TCR gamma delta, CD3, CD8, and slg. The lack of a TCR suggested NK cells, but no cytolytic activity could be detected. In addition, the cell lines constitutively produce IL-6 and can be induced to express IL-2, but not IL-4, IL-5, or IFN-gamma. Given the phenotype of these cells, it is possible that they represent T lineage precursors or some type of effector cells. Notably, CD3- CD4+ cells appear to be expanded in the spleens and livers of M. corti-infected animals, suggesting an important role in infection. Moreover, the selective growth of this cell type with M. corti hsp70 suggests that the outgrowth and in vivo expansion of these cells may be related to the stress response of the parasite.