SCID Mice Reconstituted with IL-4-deficient Lymphocytes, but Not Immunocompetent Lymphocytes, Are Resistant to Cutaneous Leishmaniasis

To characterize the roles of lymphoid- and non-lymphoid-derived IL-4 during cutaneous infection with Leishmania mexicana, the disease was monitored in SCID mice reconstituted with splenocytes from either immunocompetent BALB/c mice or IL-4-deficient BALB/c mice. Whereas following s.c. infection with L. mexicana no lesion growth was observed in BALB/c IL-4(-/-) mice and lesion growth was significantly inhibited in SCID mice, rapid initial lesion growth occurred in both SCID IL-4(+/+) and SCID IL-4(-/-) reconstituted mice. However, after 3 to 4 wk of infection, lesions in SCID IL-4(-/-) but not SCID IL-4(+/+) reconstituted mice began to heal. This paralleled a developing Th1-like phenotype and parasite clearance in the former group and a developing Th2-like phenotype in the latter group. Lesion sites from the healing SCID IL-4(-/-) mice expressed the inducible nitric oxide synthase, whereas the SCID IL-4(+/+) mice with progressive disease did not. These findings indicate that non-lymphocyte-derived IL-4 may play a role in initiating lesion growth following cutaneous infection with L. mexicana, but the presence of lymphocyte-derived IL-4 is essential for disease progression, and in its absence, lesions heal due to a developing Th1 phenotype.