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

• Published in: The Journal of immunology (1950) Vol. 169; no. 6; pp. 3232 - 3241
• Main Authors: Aseffa, Abraham, Gumy, Alain, Launois, Pascal, MacDonald, H. Robson, Louis, Jacques A, Tacchini-Cottier, Fabienne
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.2002
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.6.3232

Susceptibility and development of Th2 cells in BALB/c mice infected with Leishmania major result from early IL-4 production by Vβ4Vα8 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 107 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 107 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.