Genetic susceptibility to Leishmania: IL-12 responsiveness in TH1 cell development.
The genetic background of T lymphocytes influences development of the T helper (TH) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as Leishmania major. With an in vitro model system, a difference in maintenance of responsiveness of T cells to interleukin-12 (IL-12) was detected between BALB/c and B10.D2 mice. Although naive T cells from both strains initially responded to IL-12, BALB/c T cells lost IL-12 responsiveness after stimulation with antigen in vitro, even when cocultured with B10.D2 T cells. Thus, susceptibility of BALB/c mice to infection with L. major may derive from the loss of the ability to generate IL-12-induced TH1 responses rather than from an IL-4-induced TH2 response.
Güler
M L
ML
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gorham
J D
JD
Hsieh
C S
CS
Mackey
A J
AJ
Steen
R G
RG
Dietrich
W F
WF
Murphy
K M
KM
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma