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The Journal of Immunology, 1998, 161: 1891-1900.
Copyright © 1998 by The American Association of Immunologists

IL-4 Protects Adult C57BL/6 Mice from Prolonged Cryptosporidium parvum Infection: Analysis of CD4+{alpha}ß+IFN-{gamma}+ and CD4+{alpha}ß+IL-4+ Lymphocytes in Gut-Associated Lymphoid Tissue During Resolution of Infection1

Shirley A. Aguirre2, Lance E. Perryman{dagger}, William C. Davis* and Travis C. McGuire*

* Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164; and {dagger} Department of Microbiology, Pathology, and Parasitology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27606

Resistance of adult C57BL/6 mice to severe Cryptosporidium parvum infection is dependent on CD4+{alpha}ß+ TCR lymphocytes. In this study, we demonstrated that treatment with anti-IFN-{gamma} mAb extended oocyst excretion 18 days longer, and anti-IL-4 mAb extended oocyst excretion at least 11 days longer than isotype control mAb treatment. Analysis of the specific activity of anti-IFN-{gamma} mAb present in treated mouse sera suggested that IFN-{gamma} may have a limited role in the resolution phase of infection. Changes were also documented in numbers of CD4+{alpha}ß+IFN-{gamma}+ and CD4+{alpha}ß+IL-4+ lymphocytes in Peyer’s patches and intraepithelium of adult C57BL/6 mice during resolution of C. parvum infection. Resistance to initial severe infection was associated with CD4+{alpha}ß+IFN-{gamma}+ lymphocytes, and eventual resolution of infection was associated with CD4+{alpha}ß+IL-4+ lymphocytes. Analysis of cytokine expression following in vitro stimulation with C. parvum Ags during resolution of infection demonstrated consistent increases in CD4+{alpha}ß+IL-4+ lymphocytes, but not CD4+{alpha}ß+IFN-{gamma}+ lymphocytes. The relevance of CD4+{alpha}ß+IL-4+ lymphocytes in protection against C. parvum was then evaluated in C57BL/6 IL-4 gene knockout mice (IL-4-/-). Adult IL-4-/- mice excreted oocysts in feces approximately 23 days longer than IL-4+/+ mice. Further, anti-IFN-{gamma} mAb treatment increased the severity and the duration of infection in IL-4-/- mice compared with those in IL-4+/+ mice. Together, the data demonstrated that IFN-{gamma} was important in the control of severity of infection, and either IFN-{gamma} or IL-4 accelerated termination of infection. However, neither IL-4 nor IFN-{gamma} was required for the final clearance of infection from the intestinal tract of adult mice.




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