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ß+IFN-
+ and CD4+
ß+IL-4+ Lymphocytes in Gut-Associated Lymphoid Tissue During Resolution of Infection1

*
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164; and
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+
ß+ TCR lymphocytes. In this study, we
demonstrated that treatment with anti-IFN-
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-
mAb present in
treated mouse sera suggested that IFN-
may have a limited role in
the resolution phase of infection. Changes were also documented in
numbers of CD4+
ß+IFN-
+ and
CD4+
ß+IL-4+ lymphocytes in
Peyers patches and intraepithelium of adult C57BL/6 mice during
resolution of C. parvum infection. Resistance to initial
severe infection was associated with
CD4+
ß+IFN-
+ lymphocytes,
and eventual resolution of infection was associated with
CD4+
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+
ß+IL-4+ lymphocytes, but
not CD4+
ß+IFN-
+
lymphocytes. The relevance of
CD4+
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-
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-
was important in the
control of severity of infection, and either IFN-
or IL-4
accelerated termination of infection. However, neither IL-4 nor IFN-
was required for the final clearance of infection from the intestinal
tract of adult mice.
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