Leishmania mexicana infection induces impaired lymph node expansion and Th1 cell differentiation despite normal T cell proliferation.

Leishmania mexicana infections in C57BL/6 mice are associated with minimal immune responses and persistent cutaneous lesions. In contrast, Leishmania major elicits a robust Th1 response that promotes lesion resolution. We investigated whether the nonhealing phenotype associated with L. mexicana was due to a failure of L. mexicana to activate T cells. In vivo T cell responses to infection were assessed by tracking the behavior of labeled naive T cells following the transfer of these cells into congenic mice. Although L. mexicana infection was associated with minimal expansion of the draining lymph nodes, we observed no difference in the percentage of T cells proliferating in response to L. mexicana and L. major. Instead, differences in the size and cellularity of lymph nodes were associated with decreased recruitment of cells trafficking to the lymph node. Furthermore, we found that T cells responding to L. mexicana infection were less able to differentiate into IFN-gamma producing cells, and this deficit extended to previously activated T cells as well. Coadministration of CpG-containing oligodeoxynucleotides at the time of infection overcame this deficit and promoted disease resolution. Taken together, our results identify two distinct components that contribute to the minimal immune response associated with L. mexicana infection. First, despite ample levels of T cell proliferation, L. mexicana fails to induce substantial lymph node expansion, which limits the number of responding T cells. Second, L. mexicana infection fails to drive the differentiation of the majority of responding cells into IFN-gamma producers.