IL-7 up-regulates IL-4 production by splenic NK1.1+ and NK1.1- MHC class I-like/CD1-dependent CD4+ T cells.
NK T cells are an unusual subset of T lymphocytes. They express NK1. 1 Ag, are CD1 restricted, and highly skewed toward Vbeta8 for their TCR usage. They express the unique potential to produce large amounts of IL-4 and IFN-gamma immediately upon TCR cross-linking. We previously showed in the thymus that the NK T subset requires IL-7 for its functional maturation. In this study, we analyzed whether IL-7 was capable of regulating the production of IL-4 and IFN-gamma by the discrete NK T subset of CD4+ cells in the periphery. Two hours after injection of IL-7 into mice, or after a 4-h exposure to IL-7 in vitro, IL-4 production by CD4+ cells in response to anti-TCR-alphabeta is markedly increased. In contrast, IFN-gamma production remains essentially unchanged. In beta2-microglobulin- and CD1-deficient mice, which lack NK T cells, IL-7 treatment does not reestablish normal levels of IL-4 by CD4+ T cells. Moreover, we observe that in wild-type mice, the memory phenotype (CD62L-CD44+) CD4+ T cells responsible for IL-4 production are not only NK1.1+ cells, but also NK1.1- cells. This NK1.1-IL-4-producing subset shares three important characteristics with NK T cells: 1) Vbeta8 skewing; 2) CD1 restriction as demonstrated by their absence in CD1-deficient mice and relative overexpression in MHC II null mice; 3) sensitivity to IL-7 in terms of IL-4 production. In conclusion, the present study provides evidence that CD4+MHC class I-like-dependent T cell populations include not only NK1.1+ cells, but also NK1.1- cells, and that these two subsets are biased toward IL-4 production by IL-7.
Hameg
A
A
Institut National de la Santé et de la Recherche Médicale (INSERM), U25, Centre de l'Association Claude Bernard, Hôpital Necker, Paris, France.
Gouarin
C
C
Gombert
J M
JM
Hong
S
S
Van Kaer
L
L
Bach
J F
JF
Herbelin
A
A
D000818:Animals; D000941:Antigens / Q000502:physiology*; D018949:Antigens, CD1 / Q000502:physiology*; D000950:Antigens, Ly; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D015851:Interleukin-7 / Q000502:physiology*; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
D000941:Antigens; D018949:Antigens, CD1; D000950:Antigens, Ly; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D015851:Interleukin-7; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4