Analysis of T helper cell responses during infection with Leishmania amazonensis

Most inbred strains of mice are susceptible to Leishmania amazonensis infection and develop progressive cutaneous lesions. However, the role of Th subsets in the disease and the molecular basis of pathogenesis are unclear. To address this issue, we examined the frequency of cytokine-producing CD4⁺ T cells and the profile of αβ T cell receptor (TCR) usage in infected BALB/c mice. At different infection stages, CD4⁺ cells of draining lymph nodes contained comparable frequencies of Th1 and Th2 cells, produced comparable levels of interleukin-4 (IL-4) and interferon-γ in vitro, and showed no significant bias in αβTCR uPTCR usage. However, T cells became highly polarized to a Th2 phenotype (IL-4⁺, IL-10⁺) within a few cycles of in vitro restimulation. These Th2 cells preferentially expressed Vα2, Vβ4, or Vβ8.1/8.2, and significantly exacerbated disease in cell-transferred mice. Thus, unlike a Th2-dominant pheno-type seen in L. major infection, a mixed Th1/Th2 response can be maintained in L. amazonensis-infected mice via an as-yet-unidentified mechanism.