Circulating V?1 + T cells are activated and accumulate in the skin of systemic sclerosis patients

Giacomelli, Roberto; Matucci‐Cerinic, Marco; Cipriani, Paola; Ghersetich, Ilaria; Lattanzio, Rosangela; Pavan, Antonio; Pignone, Alberto Moggi; Cagnoni, M.; Lotti, Torello; Tonietti, G

doi:10.1002/1529-0131(199802)41:2<327::aid-art17>3.0.co;2-s

Cited by 70 publications

(24 citation statements)

References 48 publications

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“…32 Biography of human cd T cells S Kalyan and D Kabelitz 25 cells. 100,101 (and unpublished data) This occurrence is often associated with the concomitant loss of peripheral Vc9Vd2 T cells-possibly due to their tendency to undergo activation-induced cell death via FAS-mediated apoptosis which occurs following repeated stimulation of their TCR. [102][103][104] Death by exhaustion appears to be a consequence for the highly empathetic in an environment subjected to chronic distress.…”

Section: Defined By Experiences Tainted By Innate Tendenciesmentioning

confidence: 95%

“…[97][98][99][100][101] In some cases, such as systemic sclerosis, rheumatoid arthritis, Takayasu's arteritis and Wegner's granulomatosis, an inverse ratio of peripheral blood cd T cells is seen again such that the Vd1 T cell subset outnumber the Vd2 T Vd3+ (Vd5+) Figure 2 Schematic diagram of the changes in the diversity of cd T cell repertoire through development in humans. At birth, cd T cells show high junctional diversity, which is generated through the addition of 'P' (palindromic) and 'N' (nontemplated) nucleotides while combining the V-D-J segments of their TCR.…”

Section: Defined By Experiences Tainted By Innate Tendenciesmentioning

confidence: 99%

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Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

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The elusive task of defining the character of cd T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and b T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, cd T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ab T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm cd T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human cd T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses. Keywords: antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response PROLOGUE Since the time of their accidental discovery during the molecular characterization of the a and b T cell receptor (TCR) genes belonging to their relatively unambiguous brethren, 1 'enigmatic' is still one of the most commonly used adjectives to describe cd T cells. This can be attributed to the fact that these unconventional lymphocytes have thus far been remarkably successful in thwarting most attempts at definition. Much of what we know about T cell biology and function comes from what has been discerned through studies done on ab T cells; however, one thing that is certain is that the majority of the rules governing the lives of ab T cells are surprisingly irrelevant when it comes to understanding the elusive character of cd T cells. Table 1 highlights some of the major differences between these two T cell subsets in humans.Recognition by cd T cells is not typically in the context of classical major histocompatibility complex (MHC) class I or II molecules and neither is antigen processing required. 2,3 These observations are corroborated by the fact that the majority of cd T cells are CD8 and CD4 negative. Crystal structure analysis of the cd TCR determined that the length and conformation of cd TCR resemble immunoglobulins (Ig) more than the ab TCR, which was taken to suggest that antigen recognition by cd T cells may be more similar to the binding of antibody to antigen rather than the MHC/peptide complex recognized by ab T cells. 4 The very basis of foreign antigen rec...

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Section: Defined By Experiences Tainted By Innate Tendenciesmentioning

confidence: 95%

Section: Defined By Experiences Tainted By Innate Tendenciesmentioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

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“…Apart from ␣/␤ TCRϩ T cells, ␥/␦ TCRϩ T cells were found to display evidence of activation and oligoclonal expansion. An increased proportion of peripheral blood V ␦ 1 T cells exhibited activation antigens (61), and junctional region lengths were found to be skewed, which was suggestive of oligoclonal expansion of ␥/␦ TCRϩ T cells (62). Non-germline ␦-chain TCR rearrangements have also been reported (63) and suggest the presence of oligoclonal ␥/␦ TCRϩ T cells.…”

Section: T Cell Receptors (Tcrs) In Sscmentioning

confidence: 99%

Is systemic sclerosis an antigen‐driven T cell disease?

Sakkas¹,

Platsoucas²

2004

Arthritis & Rheumatism

111

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“…Several lines of evidence suggest that T cells are important in the pathogenesis of SSc, including observations that ␣/␤ and ␥/␦ T lymphocytes exhibit increased expression of activation markers (3,4), show signs of antigen-driven expansion (5), and dominate the inflammatory infiltrates in the skin and involved tissues during the early stages of the disease (6,7). T cells have been found to be necessary for the production of antitopoisomerase I antibodies in SSc (8).…”

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confidence: 99%

Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin‐13 associated with increased skin fibrosis

Fuschiotti¹,

Medsger²,

Morel³

2009

Arthritis & Rheumatism

104

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Objective. T lymphocytes play an important role in systemic sclerosis (SSc), a connective tissue disease characterized by inflammation, fibrosis, and vascular damage. While their precise role and antigen specificity are unclear, T cell-derived cytokines likely contribute to the induction of fibrosis. The aim of this study was to establish the role of cytokine dysregulation by T cells in the pathogenesis of SSc.Methods. To identify relationships between a specific cytokine, T cell subset, and the disease course, we studied a large cohort of patients with diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc). Using Luminex analysis and intracellular cytokine staining, we analyzed the intrinsic ability of CD4؉ and CD8؉ T cell subsets to produce cytokines following in vitro activation.Results. High levels of the profibrotic type 2 cytokine interleukin-13 (IL-13) were produced following activation of peripheral blood effector CD8؉ T cells from SSc patients as compared with normal controls or with patients with rheumatoid arthritis. In contrast, CD4؉ T cells showed a lower and more variable level of IL-13 production. This abnormality correlated with the extent of fibrosis and was more pronounced in dcSSc patients than in lcSSc patients. Conclusion. Dysregulated IL-13 production by effector CD8؉ T cells is important in the pathogenesis of SSc and is critical in the predisposition to more severe forms of cutaneous disease. Our study is the first to identify a specific T cell phenotype that correlates with disease severity in SSc and can be used as a marker of immune dysfunction in SSc and as a novel therapeutic target.

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Circulating V?1 + T cells are activated and accumulate in the skin of systemic sclerosis patients

Cited by 70 publications

References 48 publications

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Is systemic sclerosis an antigen‐driven T cell disease?

Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin‐13 associated with increased skin fibrosis

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