Early production of IL-4 in susceptible mice infected with Leishmania major rapidly induces IL-12 unresponsiveness.
Previous results have documented a burst of IL-4 mRNA that peaks in draining lymph nodes of susceptible BALB/c mice 16 h after infection with Leishmania major. The importance of this early IL-4 response in subsequent Th2 cell maturation is supported by observations showing that 1) neutralization of IL-4 at the initiation of infection or 2) administration of IL-12, which results in an inhibition of the 16 h IL-4 mRNA burst, inhibits Th2 cell development. However, both treatments are effective in hampering Th2 cell development only if given at a time when IL-4 has been produced for <48 h. At this time after infection, lymph node CD4+ T cells from BALB/c mice no longer respond to IL-12. This IL-12 unresponsiveness is prevented in mice treated with anti-IL-4 Abs at the initiation of infection. Finally, the inhibition of Th2 development in BALB/c mice treated with anti-IL-4 Abs at the onset of infection results from maintenance of IL-12 responsiveness, since it requires IL-12. Together, these results reveal a narrow window of time, between 16 h and <48 h after infection, during which IL-4 produced rapidly in BALB/c mice renders T cells unresponsive to IL-12, allowing their differentiation toward the Th2 phenotype.
Launois
P
P
World Health Organization Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.
Swihart
K G
KG
Milon
G
G
Louis
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007700:Kinetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4