IL-4 PROTECTS ADULT C57BL 6 MICE FROM PROLONGED CRYPTOSPORIDIUM-PARVUM INFECTION - ANALYSIS OF CD4(+)ALPHA-BETA+IFN-GAMMA(+) AND CD4(+)ALPHA-BETA+IL-4(+) LYMPHOCYTES IN GUT-ASSOCIATED LYMPHOID-TISSUE DURING RESOLUTION OF INFECTION/

Resistance of adult C57BL/6 mice to severe Cryptosporidium parvum infe ction is dependent on CD4(+)alpha beta(+) TCR lymphocytes, In this stu dy, we demonstrated that treatment with anti-IFN-gamma mAb extended oo cyst excretion 18 days longer, and anti-IL-4 mAb extended oocyst excre tion at least 11 days longer than isotype control mAb treatment. Analy sis 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 res olution phase of infection. Changes were also documented in numbers of CD4(+)alpha beta(+)IFN-gamma(+) and CD4(+)alpha beta(+)IL-4(+) lympho cytes in Peyer's patches and intraepithelium of adult C57BL/6 mice dur ing resolution of C, parvum infection. Resistance to initial severe in fection was associated with CD4(+)alpha beta(+)IFN-gamma(+) lymphocyte s, and eventual resolution of infection was associated with CD4(+)alph a beta(+)IL-4(+) lymphocytes. Analysis of cytokine expression followin g in vitro stimulation with C, parvum Ags during resolution of infecti on demonstrated consistent increases in CD4(+)alpha beta(+)IL-4(+) lym phocytes, but not CD4(+)alpha beta(+)IFN-gamma(+) lymphocytes. The rel evance of CD4(+)alpha beta(+)-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(-/-) mic e compared with those in IL-4(+/+) mice, Together, the data demonstrat ed that IFN-gamma was important in the control of severity of infectio n, and either IFN-gamma or IL-4 accelerated termination of infection. However, neither IL-4 nor IFN-gamma was required for the final clearan ce of infection from the intestinal tract of adult mice.