In susceptible mice, Leishmania major induce very rapid interleukin-4 production by CD4+ T cells which are NK1.1-.
Susceptibility of BALB/c mice to infection with Leishmania major is associated with a T helper type 2 (Th2) response. Since interleukin-4 (IL-4) is critically required early for Th2 cell development, the kinetics of IL-4 mRNA expression was compared in susceptible and resistant mice during the first days of infection. In contrast to resistant mice, susceptible mice exhibited a peak of IL-4 mRNA in their spleens 90 min after i.v. injection of parasites and in lymph nodes 16 h after s.c. injection. IL-12 and interferon-gamma (IFN-gamma) down-regulated this early peak of IL-4 mRNA; the effect of IL-12 was IFN-gamma dependent. Treatment of resistant C57BL/6 mice with anti-IFN-gamma allowed the expression of this early IL-4 response to L. major. The increased IL-4 mRNA expression occurred in V beta 8, 7, 2- CD4+ cells in BALB/c mice and NK1.1- CD4+ cells in anti-IFN-gamma treated C57BL/6 mice. These results show that the NK1.1+ CD4+ cells, responsible for the rapid burst of IL-4 production after i.v. injection of anti-CD3, do not contribute to the early IL-4 response to L. major.
Launois
P
P
WHO Immunology Research and Training Center, Institute of Biochemistry, Epalinges, Switzerland.
Ohteki
T
T
Swihart
K
K
MacDonald
H R
HR
Louis
J A
JA
D000818:Animals; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000378:metabolism* / Q000469:parasitology; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D037181:Lectins, C-Type; D018320:Leishmania major / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009500:Neutralization Tests; D011506:Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D013045:Species Specificity
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D007166:Immunosuppressive Agents; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma