Differential intra-epithelial lymphocyte phenotypes following Cryptosporidium parvum challenge in susceptible and resistant athymic strains of mice

The lack of immunocompetent laboratory animal models has limited our understanding of functional immune responses to Cryptosporidium parvum infection, but such responses have been studied in susceptible laboratory rodents with genetic, acquired, or induced immunodeficiencies. We previously observed that athymic C57BL/6J nude mice inoculated with C. parvum oocysts had lower or absent fecal oocyst excretion when compared to inoculated athymic BALB/cJ nude mice. This discrepancy prompted us to explore potential differences in intestinal immune responses in both strains. Prior to and after C. parvum challenge, BALB/cJ nude and C57BL/6J nude mice did not differ in either spleen cell numbers or in parasite-specific proliferation. However, both strains of mice exhibited a significant increase in intra-epithelial lymphocyte (IEL) numbers prior to and following C. parvum inoculation when compared to uninoculated controls (P < 0.05). Prior to challenge, C57BL/6J nude mice had a higher percentage of both CD8(+) and CD8(+)gamma delta (+) IEL than BALB/cJ nude mice. Following challenge, resistant C57BL/6J nude mice had a higher percentage of gamma delta (+), CD4(+), and CD8(+)gamma delta (+) IEL than uninoculated C57BL/6J nude mice and than susceptible BALB/cJ nude mice (P < 0.05). Conversely, inoculated C57BL/6J nude mice had a significantly lower percentage of alpha beta (+) IEL than inoculated BALB/cJ nude mice (P < 0.05). We conclude that gamma delta (+), CD4(+), and/or CD8(+)gamma delta (+) IEL may influence responses to clyptosporidiosis in athymic murine models, and that the