IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB/c mice.
BALB/c mice develop aberrant T helper 2 (Th2) responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of interleukin-4 (IL-4) early after infection. Here we demonstrate that the burst of IL-4 mRNA, peaking in draining lymph nodes of BALB/c mice 16 hr after infection, occurs within CD4+ T cells that express V beta 4 V alpha 8 T cell receptors. In contrast to control and V beta 6-deficient BALB/c mice, V beta 4-deficient BALB/c mice were resistant to infection, demonstrating the role of these cells in Th2 development. The early IL-4 response was absent in these mice, and T helper 1 responses occurred following infection. Recombinant LACK antigen from L. major induced comparable IL-4 production in V beta 4 V alpha 8 CD4+ cells. Thus, the IL-4 required for Th2 development and susceptibility to L. major is produced by a restricted population of V beta 4 V alpha 8 CD4+ T cells after cognate interaction with a single antigen from this complex organism.
Launois
P
P
World Health Organization Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.
Maillard
I
I
Pingel
S
S
Swihart
K G
KG
Xénarios
I
I
Acha-Orbea
H
H
Diggelmann
H
H
Locksley
R M
RM
MacDonald
H R
HR
Louis
J A
JA
D000818:Animals; D000953:Antigens, Protozoan / Q000494:pharmacology; D015704:CD4 Antigens / Q000032:analysis* / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology*
D000953:Antigens, Protozoan; D015704:CD4 Antigens; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C093139:LACK antigen, Leishmania; D015847:Interleukin-4