T Cell Rewiring in Differentiation and Disease

Krishnan, Sandeep; Farber, Donna L.; Tsokos, George C.

doi:10.4049/jimmunol.171.7.3325

Cited by 53 publications

(56 citation statements)

References 105 publications

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“…The increase in FcR␥ ϩ DN T cells after DLI might be due to an expansion of the naturally present subset of FcR␥ ϩ -suppressive cells or, alternatively, may be due to a transition of a subset of naive/ nonsuppressive FcR␥ Ϫ DN T cells to a suppressive FcR␥ ϩ phenotype, similar to what has been suggested for CD4 ϩ and CD8 ϩ Ag-induced Treg cells (40). This concept of transition of signaling machinery is supported by finding that FcR␥ is up-regulated in human effector CD4 ϩ T cells, but not detected in naive or memory CD4 ϩ T cells (27,41). Further studies will be required to determine at which developmental stage DN Treg cells begin to express FcR␥.…”

Section: Discussionsupporting

confidence: 65%

“…4). Reduced levels of CD3 and increased FcR␥ have been observed in human T cells from a wide array of chronic diseases such as chronic infections, autoimmune diseases (including SLE), and cancer (41). Despite the fact that this alteration may occur in pathogenic T cells, it is possible that DN Treg cells may also be serving to suppress these pathogenic cells.…”

Section: Discussionmentioning

confidence: 99%

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FcRγ Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function

Thomson

Teft

Chen

et al. 2006

The Journal of Immunology

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TCRαβ+CD4−CD8− double-negative (DN) T regulatory (Treg) cells have recently been shown to suppress Ag-specific immune responses mediated by CD8+ and CD4+ T cells in humans and mice. Our previous study using cDNA microarray analysis of global gene expression showed that FcRγ was the most highly overexpressed gene in functional DN Treg cell clones compared with nonfunctional mutant clones. In this study, we demonstrate that FcRγ-deficient DN T cells display markedly reduced suppressive activity in vitro. In addition, unlike FcRγ-sufficient DN T cells, FcRγ-deficient DN T cells were unable to prolong donor-specific allograft survival when adoptively transferred to recipient mice. Protein analyses indicate that in addition to FcRγ, DN Treg cell clones also express higher levels of TCRβ, while mutant clones expressed higher levels of Zap70 and Lck. Within DN Treg cells, we found that FcRγ associates with the TCR complex and that both FcRγ and Syk are phosphorylated in response to TCR cross-linking. Inhibition of Syk signaling and FcRγ expression were both found to reduce the suppressive function of DN Treg cells in vitro. These results indicate that FcRγ deficiency significantly impairs the ability of DN Treg cells to down-regulate allogeneic immune responses both in vitro and in vivo, and that FcRγ plays a role in mediating TCR signaling in DN Treg cells.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

FcRγ Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function

Thomson

Teft

Chen

et al. 2006

The Journal of Immunology

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“…It has previously been demonstrated that there is an increased expression many proteins responsible for defective function of CD4 + T cells [15,16,18]. These proteins include signal molecules, transcription factors, components of TCR/CD3 complex, costimulatory proteins, cytokines and molecules involved in the cytotoxic response [15,16,18].…”

Section: Discussionmentioning

confidence: 99%

“…These proteins include signal molecules, transcription factors, components of TCR/CD3 complex, costimulatory proteins, cytokines and molecules involved in the cytotoxic response [15,16,18]. PRF1 protein, with molecular mass of 60 to 75 kD, is a pore-forming molecule presented in cytotoxic lymphocytes, which execute immune mediated cell lysis [30].…”

Section: Discussionmentioning

confidence: 99%

“…It has been concluded that defective helper functions of CD4 + T cells can contribute to improper activation of B cells and autoantibody production [15][16][17][18]. Despite CD4 + T cells function mainly as helper cells, a, subpopulation of these cells also functions in an effector capacity by carrying out cytotoxicity in a peptide-specific and MHC class II-restricted mode [19].…”

Section: Introductionmentioning

confidence: 99%

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Perforin level in CD4+ T cells from patients with systemic lupus erythematosus

et al. 2010

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Human T cell clones specific for heterogeneous nuclear ribonucleoprotein A2 autoantigen from connective tissue disease patients assist in autoantibody production

Greidinger¹,

Gazitt²,

Jaimes³

et al. 2004

Arthritis & Rheumatism

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Objective. To identify and characterize human T cells reactive with heterogeneous nuclear RNP A2 (hnRNP A2) antigen, and to determine the ability of hnRNP-reactive T cells to assist in the production of human autoantibodies.Methods. T cells from patients with high serum levels of anti-hnRNP IgG autoantibody were stimulated with an hnRNP recombinant fusion protein, and the cells were cloned by limiting dilution. The surface phenotype and cytokine profiles of the T cells were examined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. T cell clones were cultured with highly purified autologous B cells, and the ability of T cells to enhance autoantibody production under a variety of conditions was measured by ELISA.Results. Human T cells reactive with hnRNP antigen were cloned from 2 patients with systemic lupus erythematosus (SLE) and 1 patient with mixed connective tissue disease (MCTD). The T cells were CD4؉ and had a Th1-like functional phenotype. In coculture in vitro with autologous B cells, T cell clones augmented anti-hnRNP autoantibody production and did so without the need for direct T cell-B cell contact.Conclusion. This study provides direct evidence for a role of anti-hnRNP-reactive T cells in autoantibody production in SLE and MCTD. These findings support the notion that hnRNP-reactive T cells play a role in the pathogenesis of these diseases.

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T Cell Rewiring in Differentiation and Disease

Cited by 53 publications

References 105 publications

FcRγ Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function

FcRγ Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function

Perforin level in CD4+ T cells from patients with systemic lupus erythematosus

Human T cell clones specific for heterogeneous nuclear ribonucleoprotein A2 autoantigen from connective tissue disease patients assist in autoantibody production

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