| As a complex, multicellular, and relatively large pathogen, Schistosoma mansoni has co-evolved with its vertebrate host to maximize its longevity and transmission while evading the host immune response. We have previously observed that parasite development is severely impaired in recombination activating gene (RAG)-1-/- mouse hosts, which lack an adaptive immune response, Schistosomes grew slower, produced fewer eggs, and did not pair as well as those in wild-type hosts. To elucidate the role of the adaptive immune response in promoting parasite development, we undertook a number of cell reconstitution and cell depletion studies. By reconstituting RAG-1-/- mice with B cells, CD8 + T cells, or CD4+ T cells prior to infection, we determined that only a CD4+ T cell population was able to rescue worm development. These observations were corroborated by data showing that depletion of CD4+ T cells in wild-type mice and subsequent infection produced an impaired growth phenotype, similar to that observed in RAG-1 -/- mice. These observations suggested that immature schistosomes must sense the host environment, in particular the immune fitness of its host, in order to initiate a period of rapid growth and sexual maturation. Specifically, we found that CD4+ alphabeta T cells were crucial in promoting parasite development.;A clear understanding of how CD4+ alphabeta T cells respond to prepatent schistosome infection is essential to elucidating the mechanism by which CD4+ T cells act to regulate parasite development. To determine the complex interactions between the schistosome and host, three lines of inquiry were undertaken. First, intracellular cytokine production by hepatic CD4+ T cells throughout early infection was analyzed. Second, T cell cytokines that may be required for parasite development were surveyed by infecting mice that possess targeted deletions in specific cytokine signaling pathways. Third, microarray experiments with both S. mansoni cDNA and oligonucleotide-based arrays were performed to analyze global gene expression patterns in developing parasites from either wildtype or immunodeficient hosts. |
