Rapid IL-4 Production by Leishmania Homolog of Mammalian RACK1-Reactive CD4 super(+) T Cells in Resistant Mice Treated Once with Anti-IL-12 or -IFN- gamma Antibodies at the Onset of Infection with Leishmania major Instructs Th2 Cell Development, Resulting in Nonhealing Lesions

• Published in: The Journal of immunology (1950) 2002-05, Vol.168 (9), p.4628-4635
• Main Authors: Launois, P, Gumy, A, Himmelrich, H, Locksley, R M, Roecken, M, Louis, JA
• Format: Article
• Language: English
• Subjects: CD4 antigen; Leishmania major; RACK1 protein
• ISSN: 0022-1767

Rapid production of IL-4 by Leishmania homolog of mammalian RACK1 (LACK)-reactive CD4 super(+) T cells expressing the V beta 4-V alpha 8 TCR chains has been shown to drive aberrant Th2 cell development and susceptibility to Leishmania major in BALB/c mice. In contrast, mice from resistant strains fail to express this early IL-4 response. However, administration of either anti-IL-12 or -IFN- gamma at the initiation of infection allows the expression of this early IL-4 response in resistant mice. In this work we show that Leishmania homolog of mammalian RACK1-reactive CD4 super(+) T cells also expressing the V beta 4-V alpha 8 TCR chains are the source of the early IL-4 response to L. major in resistant mice given anti-IL-12 or -IFN- gamma Abs only at the onset of infection. Strikingly, these cells were found to be required for the reversal of the natural resistance of C57BL/6 mice following a single administration of anti-IL-12 or -IFN- gamma Abs. Together these results suggest that a deficiency in mechanisms capable of down-regulating the early IL-4 response to L. major contributes to the exquisite susceptibility of BALB/c mice to L. major.