Notch1 expression on T cells is not required for CD4+ T helper differentiation.
Notch1 proteins are involved in binary cell fate decisions. To determine the role of Notch1 in the differentiation of CD4(+) Th1 versus Th2 cells, we have compared T helper polarization in vitro in naive CD4(+) T cells isolated from mice in which the N1 gene is specifically inactivated in all mature T cells. Following activation, Notch1-deficient CD4(+) T cells transcribed and secreted IFN-gamma under Th1 conditions and IL-4 under Th2 conditions at levels similar to that of control CD4(+) T cells. These results show that Notch1 is dispensable for the development of Th1 and Th2 phenotypes in vitro. The requirement for Notch1 in Th1 differentiation in vivo was analyzed following inoculation of Leishmania major in mice with a T cell-specific inactivation of the Notch1 gene. Following infection, these mice controlled parasite growth at the site of infection and healed their lesions. The mice developed a protective Th1 immune response characterized by high levels of IFN-gamma mRNA and protein and low levels of IL-4 mRNA with no IL-4 protein in their lymph node cells. Taken together, these results indicate that Notch1 is not critically involved in CD4(+) T helper 1 differentiation and in resolution of lesions following infection with L. major.
Tacchini-Cottier
Fabienne
F
World Health Organization Immunology Research and Training Centre, and Department of Biochemistry, University of Lausanne, Epalinges, Switzerland. Fabienne.Tacchini-Cottier@ib.unil.ch
Allenbach
Cindy
C
Otten
Luc A
LA
Radtke
Freddy
F
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D018320:Leishmania major / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014157:Transcription Factors
D000913:Antibodies, Protozoan; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D015847:Interleukin-4; D012313:RNA; D007371:Interferon-gamma