PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells

Cai, Guifang; Karni, Arnon; Oliveira, Enedina Maria Lobato de; Weiner, Howard L.; Hafler, David A.; Freeman, Gordon J.

doi:10.1016/j.cellimm.2004.09.004

Cited by 65 publications

(52 citation statements)

References 41 publications

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“…A similar phenomenon was reported by Wang and colleagues (39), i.e., blocking PD-1 in CD4 1 T cells and stimulation with antigen induced a significant increase in the release of IL-5, IL-13, granulocyte/ macrophage colony-stimulating factor, and IFN-g in vitro. Cai and colleagues (41) showed an increase in showed an increase in Th2 cytokines when the PD-1/PD-L1 and PD-L2 axis was inhibited on naive and memory T cells, but more importantly on activated CD4+ T cells using myelin basic protein. Thus, our data correlate with other reports that the blockade of PD-1 causes an increase in T-cell activation, resulting in increased Th2 cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

McGee¹,

Yagita²,

Shao³

et al. 2010

Am J Respir Cell Mol Biol

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We recently reported that the adoptive transfer of T-regulatory cells (Tregs) isolated from lung and spleen tissue of green fluorescent protein-transgenic mice reversed airway hyperresponsiveness and airway inflammation. Because Programmed Death-1 (PD-1) is a pivotal receptor regulating effector T-cell activation by Tregs, we evaluated whether PD-1 is involved in the therapeutic effect of naturally occurring Tregs (NTregs) and inducible Tregs (iTregs) in cockroach (CRA)-sensitized and challenged mice. The CD4 1 CD25 1 NTregs and CD4 1 CD25 2 iTregs isolated from the lungs and spleens of BALB/c mice were adoptively transferred into CRA-sensitized and CRA-challenged mice with and without anti-PD-1 antibody (100 mg/ mice). The CD4 1 CD25 1 T cells in the lung were phenotyped after adoptive transfer. Concentrations of IL-4, IL-5, IL-10, IFN-g, and IL-13 in bronchoalveolar lavage fluid (BALF) were measured using ELISA. The NTregs and iTregs from either lung or spleen tissue reversed airway hyperresponsiveness for at least 4 wk. However, the therapeutic effect was blocked by administering the anti-PD-1 antibody. The administration of Tregs-recipient mice with anti-PD-1 antibody significantly decreased cytotoxic T-lymphocyte antigen-4 expression, with low concentrations of Forkhead-winged transcriptional factor box 3 (Foxp3) mRNA transcripts in lung CD4 1 CD25 1 T cells. These mice had substantially higher concentrations of BALF IL-4, IL-5, and IL-13, but significantly decreased levels of BALF IL-10. Adoptive therapy recipients without the anti-PD-1 antibody exhibited high levels of CTLA-4 expression and Foxp3 transcripts in lung CD4 1 CD25 1 T cells, with a significant decrease in BALF IL-4, IL-5, and IL-13 concentrations and a substantial increase in BALF IL-10 concentrations. These data suggest that the reversal of airway hyperresponsiveness and airway inflammation by Tregs is mediated in part by PD-1, because other costimulatory molecules (e.g., inducible costimulatory molecule [ICOS] or CTLA-4) have been shown to play a role in Treg-mediated suppression.

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Section: Discussionmentioning

confidence: 99%

Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

McGee¹,

Yagita²,

Shao³

et al. 2010

Am J Respir Cell Mol Biol

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“…PD-L1 and PD-L2 are highly expressed after antigen stimulation on APCs, specifically DCs, macrophages, and B cells (12). PD-1 on T cells is the only known receptor of these ligands (12,13). Although there are reports suggesting that PD-L1 may have a stimulatory function (14), a receptor with such a function has yet to be found.…”

Section: Introductionmentioning

confidence: 98%

Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice

Gotsman

Grabie²,

DaCosta³

et al. 2007

J. Clin. Invest.

176

136

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“…Previous studies have shown that PD-1 is up-regulated upon in vitro activation of both CD4 ϩ and CD8 ϩ T cells. 54 As a result, high PD-1 expression on CFSE low CM9 ϩ CD8 ϩ T cells could be attributed either to the proliferation of preexisting PD-1 high CM9 ϩ CD8 ϩ T cells or to its de novo expression on PD-1 low CM9 ϩ CD8 ϩ T cells during their in vitro activation with the cognate peptide. To clarify this matter, sorted PD-1 high CD3 ϩ and PD-1 low CD3 ϩ were labeled with CFSE (PD-1 high ) or FarRed (PD-1 low ) and cultured for 6 days in the absence or presence of the CM9 peptide.…”

Section: Pd-1 High Siv-specific Cd8 ؉ T Cells Are Characterized By Lomentioning

confidence: 99%

SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection

Petrovas¹,

Price

Mattapallil

et al. 2007

Blood

158

169

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Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8 ؉ T-cell exhaustion. Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8 ؉ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. The majority of SIV-specific CD8 ؉ T cells expressed a PD-1 high phenotype, independent of their differentiation status, in all tissues tested. PD-1 expression gradually declined on CD8 ؉ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. SIV-specific PD-1 high CD8 ؉ T cells produced IFN-␥, TNF-␣, and IL-2 under cognate peptide stimulation. While CD8 ؉ T cells that proliferated in response to antigen had a PD-1 high phenotype, it was determined that there was a reduced proliferative capacity of PD-1 high compared with PD-1 low SIVspecific CD8 ؉ T cells. PD-1 high SIV-specific CD8 ؉ T cells were highly susceptible to IntroductionVirus-specific CD8 ϩ T cells are the predominant effectors through which the immune system controls viral infections. 1,2 While several lines of evidence indicate that human immunodeficiency virus (HIV)-specific CD8 ϩ T cells are involved in the control of HIV replication, 3-10 several reports have focused on intrinsic defects in these cells to explain their failure to clear the virus, thereby leading to progression to acquired immunodeficiency syndrome (AIDS) in all infected individuals. [11][12][13][14] Similarly, simian immunodeficiency virus (SIV)-specific CD8 ϩ T cells contribute substantially to the partial control of viremia in rhesus macaques; depletion of CD8 ϩ T cells results in increased viremia in SIV-infected animals, 15,16 while viral escape at targeted epitopes accelerates disease progression and death in vaccinated animals. 4 Furthermore, in acute SIV infection, cytotoxic SIV-specific CD8 ϩ T cells appear concurrently with the waning of early viremia. 17 As in human infection with HIV, functional defects in SIV-specific CD8 ϩ T cells have been reported, potentially explaining why virtually all SIV-infected rhesus macaques progress to simian AIDS and death despite a readily measurable CD8 ϩ T-cell response. [17][18][19][20] Therefore, understanding factors that regulate the function(s) of SIV-and HIV-specific CD8 ϩ T cells is critical in the fight against AIDS.Chronic viral infection with ongoing antigenic stimulation often results in exhaustion of virus-specific CD8 ϩ T cells. 21,22 Chronically stimulated virus-specific CD8 ϩ T cells express only low levels of receptors for IL-7 and IL-15 23 and lose the ability to maintain homeostatic proliferation. In addition, they lose the ability to produce key cytokines that are critical for the maintenance of CD8 ϩ T-cell memory. 24 In humans, the function and phenotype of chronically stimulated CD8 ϩ T cells differ among viral infections. HIV-specific CD8 ϩ T cells are less polyfunctional and more sensitive ...

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PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells

Cited by 65 publications

References 41 publications

Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice

SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection

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