The early IL-4 response to Leishmania major and the resulting Th2 cell maturation steering progressive disease in BALB/c mice are subject to the control of regulatory CD4+CD25+ T cells

J Immunol. 2002 Sep 15;169(6):3232-41. doi: 10.4049/jimmunol.169.6.3232.

Abstract

Susceptibility and development of Th2 cells in BALB/c mice infected with Leishmania major result from early IL-4 production by Vbeta4Valpha8 CD4+ T cells in response to the Leishmania homolog of mammalian RACK1 Ag. A role for CD4+CD25+ regulatory T cells in the control of this early IL-4 production was investigated by depleting in vivo this regulatory T cell population. Depletion induced an increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and protein in their lymph nodes. We further showed that transfer of 10(7) BALB/c spleen cells that were depleted of CD4+CD25+ regulatory T cells rendered SCID mice susceptible to infection and allowed Th2 differentiation while SCID mice reconstituted with 10(7) control BALB/c spleen cells were resistant to infection with L. major and developed a Th1 response. Treatment with a mAb against IL-4 upon infection with L. major in SCID mice reconstituted with CD25-depleted spleen cells prevented the development of Th2 polarization and rendered them resistant to infection. These results demonstrate that CD4+CD25+ regulatory T cells play a role in regulating the early IL-4 mRNA and the subsequent development of a Th2 response in this model of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Differentiation / immunology
  • Disease Progression
  • Disease Susceptibility / immunology
  • Female
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / immunology
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / pathology
  • Lymphocyte Activation
  • Lymphocyte Depletion / adverse effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Receptors, Interleukin-2 / biosynthesis*
  • Spleen / cytology
  • Spleen / transplantation
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology*

Substances

  • Antibodies, Monoclonal
  • Receptors, Interleukin-2
  • Interleukin-4