The IL-10 and IFN-γ pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells

Li Zhou, Hongjie Wang, Xing Zhong, Yulan Jin, Qing Sheng Mi, Ashok Kumar Sharma, Richard A McIndoe, Nikhil Garge, Robert Podolsky, Jin-Xiong She

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8+ T cells that express natural killer cell markers (CD8+ NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. Results: Large numbers of CD8+ NKT-like cells were obtained through culture of naïve CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of naïve responder T cells. Gene expression profiling suggests that the cultured CD8+ NKT-like cells and the naïve CD8+ T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8+ NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-γ. The immunosuppressive activities of cells cultured from IL-10-/- and IFN-γ-/- mice are reduced by about 70% and about 50%, respectively, compared to wild-type mice. Conclusion: Immunosuppressive CD8+ NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-γ.

Original languageEnglish (US)
Article numberR119
JournalGenome Biology
Volume9
Issue number7
DOIs
StatePublished - Jul 29 2008

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immunosuppressive agents
Natural Killer T-Cells
Immunosuppressive Agents
interleukin-10
Interleukin-10
fold
T-Lymphocytes
T-lymphocytes
gene
cells
antigen
Natural Killer Cells
gene expression
phenotype
natural killer cells
tolerance
Genes
Autoantigens
Gene Expression Profiling
Interleukin-2

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Cite this

The IL-10 and IFN-γ pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells. / Zhou, Li; Wang, Hongjie; Zhong, Xing; Jin, Yulan; Mi, Qing Sheng; Sharma, Ashok Kumar; McIndoe, Richard A; Garge, Nikhil; Podolsky, Robert; She, Jin-Xiong.

In: Genome Biology, Vol. 9, No. 7, R119, 29.07.2008.

Research output: Contribution to journalArticle

Zhou, Li ; Wang, Hongjie ; Zhong, Xing ; Jin, Yulan ; Mi, Qing Sheng ; Sharma, Ashok Kumar ; McIndoe, Richard A ; Garge, Nikhil ; Podolsky, Robert ; She, Jin-Xiong. / The IL-10 and IFN-γ pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells. In: Genome Biology. 2008 ; Vol. 9, No. 7.
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abstract = "Background: CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8+ T cells that express natural killer cell markers (CD8+ NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. Results: Large numbers of CD8+ NKT-like cells were obtained through culture of na{\"i}ve CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of na{\"i}ve responder T cells. Gene expression profiling suggests that the cultured CD8+ NKT-like cells and the na{\"i}ve CD8+ T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8+ NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-γ. The immunosuppressive activities of cells cultured from IL-10-/- and IFN-γ-/- mice are reduced by about 70{\%} and about 50{\%}, respectively, compared to wild-type mice. Conclusion: Immunosuppressive CD8+ NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-γ.",
author = "Li Zhou and Hongjie Wang and Xing Zhong and Yulan Jin and Mi, {Qing Sheng} and Sharma, {Ashok Kumar} and McIndoe, {Richard A} and Nikhil Garge and Robert Podolsky and Jin-Xiong She",
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T1 - The IL-10 and IFN-γ pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells

AU - Zhou, Li

AU - Wang, Hongjie

AU - Zhong, Xing

AU - Jin, Yulan

AU - Mi, Qing Sheng

AU - Sharma, Ashok Kumar

AU - McIndoe, Richard A

AU - Garge, Nikhil

AU - Podolsky, Robert

AU - She, Jin-Xiong

PY - 2008/7/29

Y1 - 2008/7/29

N2 - Background: CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8+ T cells that express natural killer cell markers (CD8+ NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. Results: Large numbers of CD8+ NKT-like cells were obtained through culture of naïve CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of naïve responder T cells. Gene expression profiling suggests that the cultured CD8+ NKT-like cells and the naïve CD8+ T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8+ NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-γ. The immunosuppressive activities of cells cultured from IL-10-/- and IFN-γ-/- mice are reduced by about 70% and about 50%, respectively, compared to wild-type mice. Conclusion: Immunosuppressive CD8+ NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-γ.

AB - Background: CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8+ T cells that express natural killer cell markers (CD8+ NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. Results: Large numbers of CD8+ NKT-like cells were obtained through culture of naïve CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of naïve responder T cells. Gene expression profiling suggests that the cultured CD8+ NKT-like cells and the naïve CD8+ T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8+ NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-γ. The immunosuppressive activities of cells cultured from IL-10-/- and IFN-γ-/- mice are reduced by about 70% and about 50%, respectively, compared to wild-type mice. Conclusion: Immunosuppressive CD8+ NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-γ.

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