The use of the murine model of infection with Leishmania major to reveal the antagonistic effects that IL-4 can exert on T helper cell development and demonstrate that these opposite effects depend upon the nature of the cells targeted for IL-4 signaling.
In contrast to mice from the majority of inbred strains, BALB mice develop aberrant Th2 responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of Interleukin 4, during the first 2 d of infection, by CD4+ T cells that express the Vbeta4-Valpha8 T cell receptors specific for a dominant I-A(d) restricted epitope of the LACK antigen from L. major. In contrast to this well established role of IL-4 in Th2 cell maturation, we have recently shown that, when limited to the initial period of activation of dendritic cells by L. major preceding T cell priming, IL-4 directs DCs to produce IL-12, promotes Th1 cell maturation and resistance to L. major in otherwise susceptible BALB/c mice. Thus, the antagonistic effects that IL-4 can have on Th cell development depend upon the nature of the cells (DCs or primed T cells) targeted for IL-4 signaling.
Louis
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JA
The World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of, Lausanne, Switzerland. Jacques.Louis@ib.unil.ch <Jacques.Louis@ib.unil.ch>
Gumy
A
A
Voigt
H
H
Launois
P
P
Rocken
M
M
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology* / Q000469:parasitology; D008822:Mice, Transgenic; D023421:Models, Animal; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma