CD4<sup>+</sup>PD-1<sup>+</sup>T Cells Acting as Regulatory Cells during the Induction of Anterior Chamber-Associated Immune Deviation

Quanfei, Meng; Yang, Peizeng; Li, Bing; Zhou, Hongyan; Huang, Xin; Zhu, Lei; Ren, Yalin; Kijlstra, Aize

doi:10.1167/iovs.06-0201

Cited by 38 publications

(23 citation statements)

References 46 publications

(24 reference statements)

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“…However, as we recently reported, CD25 depletion alone had no effect on tumor growth (16), suggesting that the CD4 ϩ suppressive T cell pool that we identified in the current study may be composed of other non-T regulatory suppressive cell types as well. Indeed, the existence of PD-1 ϩ CD4 T cells acting as regulatory T cells has recently been reported (36). Our preliminary data show that ICOS high CD4 T cells, purified from ϩ NKT cells exert their immunosuppressive functions through IL-13 (37,38).…”

Section: Discussionsupporting

confidence: 52%

Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation

Currie

Prosser

McDonnell

et al. 2009

The Journal of Immunology

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Tumors have evolved multiple mechanisms to evade immune destruction. One of these is expression of T cell inhibitory ligands such as programmed death-ligand 1 (PD-L1; B7-H1). In this study, we show that PD-L1 is highly expressed on mesothelioma tumor cells and within the tumor stroma. However, PD-L1 blockade only marginally affected tumor growth and was associated with the emergence of activated programmed death-1+ ICOS+ CD4 T cells in tumor-draining lymph nodes, whereas few activated CD8 T cells were present. Full activation of antitumor CD8 T cells, characterized as programmed death-1+ ICOS+ Ki-67+ and displaying CTL activity, was only observed when CD4 T cells were depleted, suggesting that a population of suppressive CD4 T cells exists. ICOS+ foxp3+ regulatory T cells were found to be regulated through PD-L1, identifying one potentially suppressive CD4 T cell population. Thus, PD-L1 blockade activates antitumor CD8 T cell most potently in the absence of CD4 T cells. These findings have implications for the development of PD-L1-based therapies.

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Section: Discussionsupporting

confidence: 52%

Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation

Currie

Prosser

McDonnell

et al. 2009

The Journal of Immunology

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“…Our earlier work has shown that CD4 + PD-1 + T cells played a potent regulatory role in ACAID. PD-1, a negative regulatory molecule in the CD28/B7 family, may be a marker for CD4 + regulatory cells [14]. In the present paper, our experiments showed that the frequency of Tregs was significantly increased in ACAID mice compared to the non-ACAID groups.…”

Section: Discussionsupporting

confidence: 61%

CD4+CD25+Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation

Zhu

Yang

Zhou

et al. 2007

Graefes Arch Clin Exp Ophthalmol

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“…In fact, PD-1 is abundantly expressed in diseases associated with increased IL-10 generation such as lung, ovary, and colon carcinoma (32,33) and HIV infection (34,35). In contrast, PD-1/ PD-L1 interactions modulate positive and negative selection in the thymus (36,37) and protect immune privileged sites such as the placenta (38,39) and the eye from immune responses (40,41).…”

Section: Discussionmentioning

confidence: 99%

Costimulatory Pathways in Multiple Sclerosis: Distinctive Expression of PD-1 and PD-L1 in Patients with Different Patterns of Disease

Trabattoni

Saresella²,

Pacei

et al. 2009

The Journal of Immunology

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T lymphocytes costimulatory molecules, including CD80, CD86, CD28, CTLA4, PD-1, PD-L1, and B7-H3, are associated with the preferential production of pro- or anti-inflammatory cytokines. We analyzed the expression of these molecules and myelin basic protein (MBP)-specific IL-10 and IFN-γ production in patients with multiple sclerosis (MS) with relapsing-remitting acute (AMS, n = 40) or stable (SMS, n = 38). Twenty-two patients successfully undergoing therapy with glatimer acetate (n = 12) or IFNβ (n = 10) were also analyzed. MBP-specific and PD-1-expressing T lymphocytes, PD-L1-expressing CD19+ cells, and PD-L1+/IL-10+/CD14+ and CD19+ cells were significantly augmented in SMS patients. Additionally, MBP-specific and annexin V-expressing CD4+ and CD8+ (apoptotic) T lymphocytes were augmented and pAkt-positive (proliferating) cells were decreased in SMS compared with AMS patients. PD-1 ligation resulted in the increase of pAkt+ lymphocytes in AMS patients alone. B7-H3 expression and IFN-γ production were comparable in all individuals but the PD-L1+/IL-10+ over B7-H3+/IFN-γ+ ratio was significantly lower in AMS compared with SMS patients. Finally, PD-L1 expression on immune cells was reduced in treated patients, suggesting that therapy-induced disease remission is not associated with the modulation of the expression of this molecule. The PD-1/PD-L1 pathway plays an important role in modulating immune functions in MS patients; monitoring and targeting these proteins could offer diagnostic and therapeutic advantages.

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CD4⁺PD-1⁺T Cells Acting as Regulatory Cells during the Induction of Anterior Chamber-Associated Immune Deviation

Cited by 38 publications

References 46 publications

Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation

Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation

CD4+CD25+Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation

Costimulatory Pathways in Multiple Sclerosis: Distinctive Expression of PD-1 and PD-L1 in Patients with Different Patterns of Disease

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CD4+PD-1+T Cells Acting as Regulatory Cells during the Induction of Anterior Chamber-Associated Immune Deviation

Cited by 38 publications

References 46 publications

Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation

Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation

CD4+CD25+Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation

Costimulatory Pathways in Multiple Sclerosis: Distinctive Expression of PD-1 and PD-L1 in Patients with Different Patterns of Disease

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CD4⁺PD-1⁺T Cells Acting as Regulatory Cells during the Induction of Anterior Chamber-Associated Immune Deviation