Abstract
B cells are exposed to high levels of CD40 ligand (CD40L, CD154) in chronic inflammatory diseases. In addition, B cells expressing both CD40 and CD40L have been identified in human diseases such as autoimmune diseases and lymphoma. However, how such constitutively CD40-activated B cells under inflammation may impact on T cell response remains unknown. Using a mouse model in which B cells express a CD40L transgene (CD40LTg) and receive autocrine CD40/CD40L signaling, we show that CD40LTg B cells stimulated memory-like CD4 and CD8 T cells to express IL-10. This IL-10 expression by CD8 T cells was dependent on IFN-I and programmed cell death protein 1, and was critical for CD8 T cells to counterregulate their overactivation. Furthermore, adoptive transfer of naive CD8 T cells in RAG-1-/- mice normally induces colitis in association with IL-17 and IFN-γ cytokine production. Using this model, we show that adoptive cotransfer of CD40LTg B cells, but not wild-type B cells, significantly reduced IL-17 response and regulated colitis in association with IL-10 induction in CD8 T cells. Thus, B cells expressing CD40L can be a therapeutic goal to regulate inflammatory CD8 T cell response by IL-10 induction.
Original language | English (US) |
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Pages (from-to) | 3189-3196 |
Number of pages | 8 |
Journal | Journal of Immunology |
Volume | 190 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 2013 |
Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction. / Koni, Pandelakis A.; Bolduc, Anna; Takezaki, Mayuko; Ametani, Yutetsu; Huang, Lei; Lee, Jeffrey R.; Nutt, Stephen L.; Kamanaka, Masahito; Flavell, Richard A.; Mellor, Andrew L.; Tsubata, Takeshi; Shimoda, Michiko.
In: Journal of Immunology, Vol. 190, No. 7, 01.04.2013, p. 3189-3196.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction
AU - Koni, Pandelakis A.
AU - Bolduc, Anna
AU - Takezaki, Mayuko
AU - Ametani, Yutetsu
AU - Huang, Lei
AU - Lee, Jeffrey R.
AU - Nutt, Stephen L.
AU - Kamanaka, Masahito
AU - Flavell, Richard A.
AU - Mellor, Andrew L.
AU - Tsubata, Takeshi
AU - Shimoda, Michiko
PY - 2013/4/1
Y1 - 2013/4/1
N2 - B cells are exposed to high levels of CD40 ligand (CD40L, CD154) in chronic inflammatory diseases. In addition, B cells expressing both CD40 and CD40L have been identified in human diseases such as autoimmune diseases and lymphoma. However, how such constitutively CD40-activated B cells under inflammation may impact on T cell response remains unknown. Using a mouse model in which B cells express a CD40L transgene (CD40LTg) and receive autocrine CD40/CD40L signaling, we show that CD40LTg B cells stimulated memory-like CD4 and CD8 T cells to express IL-10. This IL-10 expression by CD8 T cells was dependent on IFN-I and programmed cell death protein 1, and was critical for CD8 T cells to counterregulate their overactivation. Furthermore, adoptive transfer of naive CD8 T cells in RAG-1-/- mice normally induces colitis in association with IL-17 and IFN-γ cytokine production. Using this model, we show that adoptive cotransfer of CD40LTg B cells, but not wild-type B cells, significantly reduced IL-17 response and regulated colitis in association with IL-10 induction in CD8 T cells. Thus, B cells expressing CD40L can be a therapeutic goal to regulate inflammatory CD8 T cell response by IL-10 induction.
AB - B cells are exposed to high levels of CD40 ligand (CD40L, CD154) in chronic inflammatory diseases. In addition, B cells expressing both CD40 and CD40L have been identified in human diseases such as autoimmune diseases and lymphoma. However, how such constitutively CD40-activated B cells under inflammation may impact on T cell response remains unknown. Using a mouse model in which B cells express a CD40L transgene (CD40LTg) and receive autocrine CD40/CD40L signaling, we show that CD40LTg B cells stimulated memory-like CD4 and CD8 T cells to express IL-10. This IL-10 expression by CD8 T cells was dependent on IFN-I and programmed cell death protein 1, and was critical for CD8 T cells to counterregulate their overactivation. Furthermore, adoptive transfer of naive CD8 T cells in RAG-1-/- mice normally induces colitis in association with IL-17 and IFN-γ cytokine production. Using this model, we show that adoptive cotransfer of CD40LTg B cells, but not wild-type B cells, significantly reduced IL-17 response and regulated colitis in association with IL-10 induction in CD8 T cells. Thus, B cells expressing CD40L can be a therapeutic goal to regulate inflammatory CD8 T cell response by IL-10 induction.
UR - http://www.scopus.com/inward/record.url?scp=84875471692&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875471692&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1203364
DO - 10.4049/jimmunol.1203364
M3 - Article
C2 - 23440421
AN - SCOPUS:84875471692
VL - 190
SP - 3189
EP - 3196
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -