Antigen-Responsive CD4 + T Cells from C3H Mice Chronically Infected with Leishmania amazonensis Are Impaired in the Transition to an Effector Phenotype

Abstract

ABSTRACT C3HeB/FeJ mice challenged with Leishmania major develop a polarized Th1 response and subsequently heal, whereas Leishmania amazonensis challenge leads to chronic lesions with high parasite loads at 10 weeks postinfection. In this study, a comparison of draining lymph node cells from L. amazonensis - and L. major -infected mice at 10 weeks postinfection showed equivalent percentages of effector/memory phenotype CD44 hi CD4 + T cells producing interleukin-2 (IL-2) and proliferating after antigen stimulation. However, these cells isolated from L. amazonensis -infected mice were not skewed toward either a Th1 or Th2 phenotype in vivo, as evidenced by their unbiased Th1/Th2 transcription factor mRNA profile. In vivo antigen stimulation with added IL-12 failed to enhance gamma interferon (IFN-γ) production of CD4 + T cells from L. amazonensis -infected mice. Antigen stimulation of CD4 + T cells from L. amazonensis -infected mice in vitro in the presence of IL-12 resulted in production of only 10 to 15% of the IFN-γ produced by T cells from L. major -infected mice under identical conditions. These results suggest that the CD4 + T-cell response during chronic L. amazonensis infection is limited during the transition from an early activated CD4 + T-cell population to an effector cell population and demonstrate that these T cells have an intrinsic defect beyond the presence or absence of IL-12 during antigen stimulation.