title: CD4+ T cells are not essential for control of early acute Cryptosporidium parvum infection in neonatal mice.
abstract: Cryptosporidiosis is an important diarrheal disease of humans and neonatal livestock caused by Cryptosporidium spp. that infect epithelial cells. Recovery from Cryptosporidium parvum infection in adult hosts involves CD4(+) T cells with a strong Th1 component, but mechanisms of immunity in neonates are not well characterized. In the present investigation with newborn mice, similar acute patterns of infection were obtained in C57BL/6 wild-type (WT) and T and B cell-deficient Rag2(-/-) mice. In comparison with uninfected controls, the proportion of intestinal CD4(+) or CD8(+) T cells did not increase in infected WT mice during recovery from infection. Furthermore, infection in neonatal WT mice depleted of CD4(+) T cells was not exacerbated. Ten weeks after WT and Rag2(-/-) mice had been infected as neonates, no patent infections could be detected. Treatment at this stage with the immunosuppressive drug dexamethasone produced patent infections in Rag2(-/-) mice but not WT mice. Expression of inflammatory markers, including gamma interferon (IFN-γ) and interleukin-12p40 (IL-12p40), was higher in neonatal WT mice than in Rag2(-/-) mice around the peak of infection, but IL-10 expression was also higher in WT mice. These results suggest that although CD4(+) T cells may be important for elimination of C. parvum, these cells are dispensable for controlling the early acute phase of infection in neonates.
authors.affiliation: Barts and the London School of Medicine and Dentistry, Centre for Digestive Diseases, Blizard Institute of Cell and Molecular Science, Queen Mary University of London, London, UK.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Korbel
authors.forename: Farah M
authors.initials: FM
authors.lastname: Barakat
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: Vincent
authors.initials: V
authors.lastname: McDonald
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003457:Cryptosporidiosis / Q000276:immunology* / Q000473:pathology*; D016785:Cryptosporidium parvum / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse