LACK-reactive CD4+ T cells require autocrine IL-2 to mediate susceptibility to Leishmania major.
Mice from most inbred strains are resistant to infection with Leishmania major whereas mice from BALB strains are highly susceptible. Resistance and susceptibility result from the development of Th1 or Th2 cells, respectively. In this report, we document an IL-2 mRNA burst, preceding the reported early IL-4 response, in draining lymph nodes of susceptible mice infected with L. major. Neutralization of IL-2 during the first days of infection redirected Th1 cell maturation and resistance to L. major, through interference with the rapid IL-4 transcription in Leishmania homolog of mammalian RACK1 (LACK)-reactive CD4(+) cells. A burst of IL-2 transcripts also occurred in infected C57BL/6 mice that do not mount an early IL-4 response. However, although the LACK protein induced IL-2 transcripts in susceptible mice, it failed to trigger this response in resistant C57BL/6 mice. Reconstitution experiments using C.B.-17 SCID mice and LACK-reactive CD4(+) T cells from IL-2(-/-) BALB/c mice showed that triggering of the early IL-4 response required autocrine IL-2. Thus, in C57BL/6 mice, the inability of LACK-reactive CD4(+) T cells to express early IL-4 mRNA transcription, important for disease progression, appears due to an incapacity of these cells to produce IL-2.
Gumy
Alain
A
World Health Organization Immunology Research and Training Centre, University of Lausanne, Epalinges, Switzerland.
Aseffa
Abraham
A
Rachinel
Nicolas
N
Breton
Melanie
M
Otten
Luc
L
Tacchini-Cottier
Fabienne
F
Röcken
Martin
M
Doyen
Noelle
N
Acha-Orbea
Hans
H
Locksley
Richard M
RM
MacDonald
H Robson
HR
Launois
Pascal
P
Louis
Jacques
J
D019264:Adoptive Transfer; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D004198:Disease Susceptibility; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D015800:Protozoan Proteins / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms
D000953:Antigens, Protozoan; D007376:Interleukin-2; D015800:Protozoan Proteins; D012333:RNA, Messenger; C093139:LACK antigen, Leishmania; D015847:Interleukin-4