Rapid expansion and IL-4 expression by Leishmania-specific naive helper T cells in vivo.
CD4 T cells are pivotal for effective immunity, yet their initial differentiation into effector subsets after infection remains poorly defined. We examined CD4 T cells specific for the immunodominant Leishmania major LACK antigen using MHC/peptide tetramers and IL-4 reporter mice. Comprising approximately 15 cells/lymph node in naive mice, LACK-specific T cells expanded over 100-fold, and 70% acquired IL-4 expression by 96 hr. Despite their pathogenic role in susceptible mice, LACK-specific precursor frequency, expansion, and IL-4 expression were comparable between susceptible and resistant mice. When injected with unrelated antigen, Leishmania efficiently activated IL-4 expression from naive antigen-specific T cells. CD4 subset polarization in this highly characterized model occurs independently from IL-4 expression by naive T cells, which is activated indiscriminately after parasitism.
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, 94143, USA.
Daniel B
DB
Stetson
Markus
M
Mohrs
Valerie
V
Mallet-Designe
Luc
L
Teyton
Richard M
RM
Locksley
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000235:genetics*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D016056:Immunodominant Epitopes; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania; D015847:Interleukin-4