Splenic T cells from mice receiving intracameral antigen suppress in-vitro antigen-induced proliferation and interferon-? production by sensitized lymph node cells

Ghali, Wael; Pingle, Pavani; Traboulsi, Amar; Dalal, Tajas; O’Rourke, James; Cone, Robert E.

doi:10.1076/ocii.11.1.39.15578

Cited by 10 publications

(13 citation statements)

References 6 publications

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“…This observation was based on a previous finding, demonstrating that CD8 + T‐cell‐mediated suppression in certain models depends upon IFN‐γ production in order to elaborate TGF‐β activity 21 . In addition, CD8 + AC‐SPL cells do produce TGF‐β but do not produce IL‐10 31 . Nevertheless, Kezuka & Streilen reported that CD8 + suppressor T cells are produced in FasL –/– mice 32 .…”

Section: Discussionmentioning

confidence: 95%

The suppression of delayed‐type hypersensitivity by CD8⁺ regulatory T cells requires interferon‐γ

Cone¹,

Li²,

Sharafieh³

et al. 2007

Immunology

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Summary CD8+ regulatory (suppressor) T cells are induced by complex cellular pathways in the spleens of mice that have received an injection of antigen into the anterior chamber (AC) of an eye, an immune‐privileged site. Although these CD8+ regulatory T cells perform an antigen‐specific regulatory function for an immune response to self and non‐self antigens, the mechanisms of the activation or function of these regulatory cells are not clear. Here, we describe a novel mechanism for the activation of splenic CD8+ regulatory T cells induced by injection of antigen into the AC. Immunization of mice with trinitrophenyl and bovine serum albumin (TNP‐BSA) amplified AC‐induced splenic CD8+ regulatory T cells that suppressed the initiation of contact sensitivity when transferred to immunized, challenged mice. These CD8+ regulatory T cells were produced independently of perforin, indicating that they are not canonical cytotoxic T cells. Fas ligand (FasL)‐deficient CD8+ regulatory T‐cell function was rescued by inclusion of exogenous interferon‐γ (IFN‐γ), demonstrating that the expression of FasL by CD8+ regulatory T cells was dispensable, but IFN‐γ was not. Ultimately, we demonstrated that the generation of these CD8+ regulatory T cells occurred independently of IFN‐γ, but their suppressor function required IFN‐γ receptor stimulation.

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Section: Discussionmentioning

confidence: 95%

The suppression of delayed‐type hypersensitivity by CD8⁺ regulatory T cells requires interferon‐γ

Cone¹,

Li²,

Sharafieh³

et al. 2007

Immunology

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“…Splenic CD8 + T cells induced by the intracameral injection of antigen suppress the transfer of DTH in vivo by sensitized T cells 6 , 7 , 12 , 14 and antigen‐induced T‐cell proliferation and interferon‐γ (IFN‐γ) production in vitro . 23 , 24 , 25 , 26 The LTS assay measures the suppression of a DTH reaction in immunized recipients by the transfer of CD8 + regulatory T cells but not naive spleen cells to the site challenged by antigen. We used this in vivo demonstration of the suppression of DTH by injected AC‐SPL cells because this is analogous to the suppression of DTH reaction by the injection of antigen into the AC.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of suppression of a DTH reaction by the CD8 + regulatory effector AC‐SPL cells is not known. However, there are reports that suggest that CD8 + regulatory effector cells produce immunosuppressive TGF‐β 23 , 30 , 31 , 32 . The suppression of TCR‐mediated proliferation of T cells in vitro by CD8 + regulatory cells induced by the intracameral injection of antigen is partially inhibited by antibodies to TGF‐β1 32 .…”

Section: Discussionmentioning

confidence: 99%

“…However, there are reports that suggest that CD8 + regulatory effector cells produce immunosuppressive TGF-b. 23,[30][31][32] The suppression of TCR-mediated proliferation of T cells in vitro by CD8 + regulatory cells induced by the intracameral injection of antigen is partially inhibited by antibodies to TGF-b1. 32 We have observed that antibodies to TGF-b1, 2, 3 completely inhibit the suppression of DTH by CD8 + AC-SPL cells in the LTS (RE Cone et al, submitted for publication).…”

Section: Discussionmentioning

confidence: 99%

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The suppression of hypersensitivity by ocular‐induced CD8⁺T cells requires compatibility in the Qa‐1 haplotype

et al. 2009

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The injection of antigen into the anterior chamber (AC, intracameral injection)2 of a murine eye induces the generation of splenic CD8+ regulatory T cells (AC-SPL cells) that effect the antigen-specific suppression of a Delayed-Type Hypersensitivity (DTH) reaction. Here we show (i) for the first time that the local antigen-specific suppression of DTH-induced swelling in immunized mice by either an intracameral injection of antigen or by the direct injection of CD8+ AC-SPL cells into an antigen-challenged site is associated with an absence of infiltrated mononuclear cells, (ii) the local antigen-specific suppression of the DTH reaction by CD8+ AC-SPL cells requires compatibility between the Qa-1 but not H2 antigen haplotype of the immunized recipient and the injected AC-SPL regulatory T cells, (iii) The suppression of the DTH reaction by CD8+ AC-SPL cells requires the expression of Qa-1 but not H2 antigens and is not due to bystander suppression.

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“…TGF-β and IL-10 have been shown to be the suppressive cytokines in immune tolerance models including ACAID [13][14][15][16][17][18][19][20][21][22]. TGF-β1, a major component of the TGF-β family, along with TGF-β2 has been proven to be involved in the immunoregulation.…”

Section: Discussionmentioning

confidence: 99%

Splenic CD8+ T cells secrete TGF-β1 to exert suppression in mice with anterior chamber-associated immune deviation

Jiang¹,

He²,

Yang

et al. 2008

Graefes Arch Clin Exp Ophthalmol

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Background CD8+ regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The mechanisms of suppression by CD8+ T cells in ACAID remain only poorly understood. TGF-beta1 is considered as an inhibitory cytokine for immunosuppression in some models. The production of TGF-beta1 by CD8+ T cells in ACAID, and whether CD8+ T cells exert suppression through TGF-beta1, is unknown. Methods The suppressive effect of CD8+ T cells in ACAID mice was determined by a local adoptive transfer (LAT) assay. The production of TGF-beta1 by CD8+ T cells was measured by enzyme-linked immunosorbent assay (ELISA). Anti-TGF-beta1 antibodies were used in the LAT assay to test if they could block the inhibitory effect of CD8+ T cells. Results CD8+ T cells from ACAID mice were shown to block the delayed-type hypersensitivity (DTH) response in an antigen-specific manner in a LAT assay. These CD8+ T cells secreted TGF-beta1, and their suppression could partially be blocked by anti-TGF-beta1 antibodies. Conclusions Our study confirms that CD8+ T cells from ACAID mice possess inhibitory properties. This population exerts part of its suppressive function via the production of TGF-beta1.

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Splenic T cells from mice receiving intracameral antigen suppress in-vitro antigen-induced proliferation and interferon-? production by sensitized lymph node cells

Cited by 10 publications

References 6 publications

The suppression of delayed‐type hypersensitivity by CD8⁺ regulatory T cells requires interferon‐γ

The suppression of delayed‐type hypersensitivity by CD8⁺ regulatory T cells requires interferon‐γ

The suppression of hypersensitivity by ocular‐induced CD8⁺T cells requires compatibility in the Qa‐1 haplotype

Splenic CD8+ T cells secrete TGF-β1 to exert suppression in mice with anterior chamber-associated immune deviation

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Splenic T cells from mice receiving intracameral antigen suppress in-vitro antigen-induced proliferation and interferon-? production by sensitized lymph node cells

Cited by 10 publications

References 6 publications

The suppression of delayed‐type hypersensitivity by CD8+ regulatory T cells requires interferon‐γ

The suppression of delayed‐type hypersensitivity by CD8+ regulatory T cells requires interferon‐γ

The suppression of hypersensitivity by ocular‐induced CD8+T cells requires compatibility in the Qa‐1 haplotype

Splenic CD8+ T cells secrete TGF-β1 to exert suppression in mice with anterior chamber-associated immune deviation

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The suppression of delayed‐type hypersensitivity by CD8⁺ regulatory T cells requires interferon‐γ

The suppression of delayed‐type hypersensitivity by CD8⁺ regulatory T cells requires interferon‐γ

The suppression of hypersensitivity by ocular‐induced CD8⁺T cells requires compatibility in the Qa‐1 haplotype