Abstract
In a model of systemic tolerance called Anterior Chamber-Associated Immune Deviation (ACAID), the differentiation of the T regulatory (Tr) cells depends on NK T cells and occurs in the spleen. We now show that the CD1d-reactive NK T cell subpopulation, required for development of systemic tolerance, expresses the invariant Vα14Jα281 TCR because Jα281 knockout (KO) mice were unable to generate Ag-specific Tr cells and ACAID. The mechanism for NK T cell-dependent differentiation of Ag-specific Tr cells mediating systemic tolerance was studied by defining the cytokine profiles in heterogeneous and enriched NK T spleen cells. In contrast to there being no differences in most regulatory cytokine mRNAs, both mRNA and protein for IL-10 were increased in splenic NK T cells of anterior chamber (a.c.)-inoculated mice. However, IL-10 mRNA was not increased in spleens after i.v. inoculation. Finally, NK T cells from wild-type (WT) mice, but not from IL-10 KO mice, reconstituted the ACAID inducing ability in Jα281 KO mice. Thus, NK T cell-derived IL-10 is critical for the generation of the Ag-specific Tr cells and systemic tolerance induced to eye-inoculated Ags.
| Original language | English |
|---|---|
| Pages (from-to) | 42-50 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 166 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2001 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Immunology
Cite this
NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. / Sonoda, Kohei; Faunce, D. E.; Taniguchi, M.; Exley, M.; Balk, S.; Stein-Streilein, J.
In: Journal of Immunology, Vol. 166, No. 1, 01.01.2001, p. 42-50.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance
AU - Sonoda, Kohei
AU - Faunce, D. E.
AU - Taniguchi, M.
AU - Exley, M.
AU - Balk, S.
AU - Stein-Streilein, J.
PY - 2001/1/1
Y1 - 2001/1/1
N2 - In a model of systemic tolerance called Anterior Chamber-Associated Immune Deviation (ACAID), the differentiation of the T regulatory (Tr) cells depends on NK T cells and occurs in the spleen. We now show that the CD1d-reactive NK T cell subpopulation, required for development of systemic tolerance, expresses the invariant Vα14Jα281 TCR because Jα281 knockout (KO) mice were unable to generate Ag-specific Tr cells and ACAID. The mechanism for NK T cell-dependent differentiation of Ag-specific Tr cells mediating systemic tolerance was studied by defining the cytokine profiles in heterogeneous and enriched NK T spleen cells. In contrast to there being no differences in most regulatory cytokine mRNAs, both mRNA and protein for IL-10 were increased in splenic NK T cells of anterior chamber (a.c.)-inoculated mice. However, IL-10 mRNA was not increased in spleens after i.v. inoculation. Finally, NK T cells from wild-type (WT) mice, but not from IL-10 KO mice, reconstituted the ACAID inducing ability in Jα281 KO mice. Thus, NK T cell-derived IL-10 is critical for the generation of the Ag-specific Tr cells and systemic tolerance induced to eye-inoculated Ags.
AB - In a model of systemic tolerance called Anterior Chamber-Associated Immune Deviation (ACAID), the differentiation of the T regulatory (Tr) cells depends on NK T cells and occurs in the spleen. We now show that the CD1d-reactive NK T cell subpopulation, required for development of systemic tolerance, expresses the invariant Vα14Jα281 TCR because Jα281 knockout (KO) mice were unable to generate Ag-specific Tr cells and ACAID. The mechanism for NK T cell-dependent differentiation of Ag-specific Tr cells mediating systemic tolerance was studied by defining the cytokine profiles in heterogeneous and enriched NK T spleen cells. In contrast to there being no differences in most regulatory cytokine mRNAs, both mRNA and protein for IL-10 were increased in splenic NK T cells of anterior chamber (a.c.)-inoculated mice. However, IL-10 mRNA was not increased in spleens after i.v. inoculation. Finally, NK T cells from wild-type (WT) mice, but not from IL-10 KO mice, reconstituted the ACAID inducing ability in Jα281 KO mice. Thus, NK T cell-derived IL-10 is critical for the generation of the Ag-specific Tr cells and systemic tolerance induced to eye-inoculated Ags.
UR - http://www.scopus.com/inward/record.url?scp=0035172782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035172782&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.166.1.42
DO - 10.4049/jimmunol.166.1.42
M3 - Article
C2 - 11123275
AN - SCOPUS:0035172782
VL - 166
SP - 42
EP - 50
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -