Characterization of mouse CD4 T cell subsets defined by expression of KLRG1

Beyersdorf, Niklas; Ding, Xin; Tietze, Julia K.; Hanke, Thomas

doi:10.1002/eji.200737126

Cited by 75 publications

(63 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the canonical signature of bulk Treg cells, defined by us and others, is really a composite derived from cells of diverse subphenotypes. Certainly, there is precedent for the subphenotypes observed here, as variability in the surface expression of CD103, Klrg1, or Cxcr3 and corresponding functional diversity have been described previously (38)(39)(40)(41).…”

Section: Discussionsupporting

confidence: 61%

Genomic definition of multiple ex vivo regulatory T cell subphenotypes

Feuerer

Hill

Kretschmer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

199

196

View full text Add to dashboard Cite

Regulatory T (Treg) cells that express the Foxp3 transcription factor are essential for lymphoid homeostasis and immune tolerance to self. Other nonimmunological functions of Treg cells, such as controlling metabolic function in adipose tissue, are also emerging. Treg cells originate primarily in the thymus, but can also be elicited from conventional T cells by in vivo exposure to low-dose antigen or homeostatic expansion or by activation in the presence of TGFβ in vitro. Treg cells are characterized by a distinct transcriptional signature controlled in part, but not solely, by Foxp3. For a better perspective on transcriptional control in Treg cells, we compared gene expression profiles of a broad panel of Treg cells from various origins or anatomical locations. Treg cells generated by different means form different subphenotypes and were identifiable by particular combinations of transcripts, none of which fully encompassed the entire Treg signature. Molecules involved in Treg cell effector function, chemokine receptors, and the transcription factors that control them were differentially represented in these subphenotypes. Treg cells from the gut proved dissimilar to cells elicited by exposure to TGFβ in vitro, but instead they resembled a CD103 + Klrg1 + subphenotype preferentially generated in response to lymphopenia.

show abstract

Section: Discussionsupporting

confidence: 61%

Genomic definition of multiple ex vivo regulatory T cell subphenotypes

Feuerer

Hill

Kretschmer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

199

196

View full text Add to dashboard Cite

show abstract

“…In addition to CTLA-4 and PD-1, expression of 4-1BB and KLRG1 has been associated with enhanced Treg function (17,18). In each case, we found that combination blockade of the CTLA-4 and PD-1 pathways significantly decreased the fraction of Tregs expressing the relevant activation marker (Fig.…”

Section: Combination Coinhibitory Receptor Blockade Decreases Expressmentioning

confidence: 62%

PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors

Curran

Montalvo

Yagita

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

1,642

1,268

View full text Add to dashboard Cite

Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. Adding αPD-L1 to this regimen results in rejection of 65% of preimplanted tumors vs. 10% with CTLA-4 blockade alone. Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. Combination blockade also synergistically increases Teff-to-myeloid-derived suppressor cell ratios within B16 melanomas. IFN-γ production increases in both the tumor and vaccine draining lymph nodes, as does the frequency of IFN-γ/TNF-α double-producing CD8 + T cells within the tumor. These results suggest that combination blockade of the PD-1/ PD-L1-and CTLA-4-negative costimulatory pathways allows tumorspecific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory.he interaction between the T-cell receptor complex (TCR) and antigenic peptides bound in surface MHC molecules provides the specificity that defines adaptive T-cell immunity. In addition to TCR activation, costimulation via ligation of the coreceptor CD28 on T cells by B7 molecules on antigenpresenting cells (APCs) is required for optimal T-cell activation (1). Once mobilized, however, T cells begin to express other members of the CD28/B7 receptor family that attenuate the immune response through inhibition of proliferation and cytokine production (2). Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is rapidly up-regulated following T-cell activation and binds to B7 molecules with a higher affinity than does CD28. The receptor programmed death-1 (PD-1) is also expressed on T cells following activation, where, on binding to its ligands PD-L1 and PD-L2, it promotes T-cell anergy, apoptosis, and exhaustion. Recently, an additional coinhibitory ligand/receptor interaction has been described that involves binding of PD-L1 on T cells to B7-1 on APCs or vice versa (3). Although the existence of so many layers of T-cell inhibition may seem surprising, the severe and sometimes fatal autoimmunity that results when even one of these pathways is disrupted attests to their necessity.Malignant transformation was classically defined by the ability to avoid the norm...

show abstract

“…Furthermore, within the Treg population isolated from infected mice, cluster analysis revealed that exclusively 64 genes were upregulated and 50 genes were downregulated when compared with Tregs isolated from naive mice. Interestingly, within this cluster we did not find gene expression of classical Treg markers such as IL-10 or TGF-b, but rather granzyme B, secretory leukoprotease inhibitor 1 (Slpi), metallothionein-1 (Mt1) and killer cell lectin-like receptor G1 (Klrg1), effector molecules implied in the literature to be involved in regulating inflammatory processes (21)(22)(23)(24).…”

mentioning

confidence: 88%

Pronounced Phenotype in Activated Regulatory T Cells during a Chronic Helminth Infection

Layland

Mages

Loddenkemper

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Although several markers have been associated with the characterization of regulatory T cells (Tregs) and their function, no studies have investigated the dynamics of their phenotype during infection. Since the necessity of Tregs to control immunopathology has been demonstrated, we used the chronic helminth infection model Schistosoma mansoni to address the impact on the Treg gene repertoire. Before gene expression profiling, we first studied the localization and Ag-specific suppressive nature of classically defined Tregs during infection. The presence of Foxp3+ cells was predominantly found in the periphery of granulomas and isolated CD4+CD25hiFoxp3+ Tregs from infected mice and blocked IFN-γ and IL-10 cytokine secretion from infected CD4+CD25− effector T cells. Furthermore, the gene expression patterns of Tregs and effector T cells showed that 474 genes were significantly regulated during schistosomiasis. After k-means clustering, we identified genes exclusively regulated in all four populations, including Foxp3, CD103, GITR, OX40, and CTLA-4—classic Treg markers. During infection, however, several nonclassical genes were upregulated solely within the Treg population, such as Slpi, Gzmb, Mt1, Fabp5, Nfil3, Socs2, Gpr177, and Klrg1. Using RT-PCR, we confirmed aspects of the microarray data and also showed that the expression profile of Tregs from S. mansoni-infected mice is simultaneously unique and comparable with Tregs derived from other infections.

show abstract

Characterization of mouse CD4 T cell subsets defined by expression of KLRG1

Abstract: The mouse killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor known to be expressed on a subset of NK cells and antigen-experienced CD8 T cells.

Cited by 75 publications

References 43 publications

Genomic definition of multiple ex vivo regulatory T cell subphenotypes

Genomic definition of multiple ex vivo regulatory T cell subphenotypes

PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors

Pronounced Phenotype in Activated Regulatory T Cells during a Chronic Helminth Infection

Contact Info

Product

Resources

About