Antigen-responsive CD4+ T cells from C3H mice chronically infected with Leishmania amazonensis are impaired in the transition to an effector phenotype.
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 CD44hi 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-gamma) 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-gamma 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.
Immunobiology Program, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
Amanda E
AE
Ramer
Yannick F
YF
Vanloubbeeck
Douglas E
DE
Jones
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D018664:Interleukin-12 / Q000378:metabolism; D007891:Leishmania / Q000737:chemistry; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010641:Phenotype
D015704:CD4 Antigens; D018664:Interleukin-12