Gamma-Delta T Cells: Immunoregulatory Functions and Immunoprotection

Cai, Jianshu; Tucker, Philip W.

doi:10.1159/000058827

Cited by 20 publications

(28 citation statements)

References 197 publications

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“…We have previously shown an increase d percentage in immun odeficient anima ls (R2 l) of CD8aa homodimer iIEL, as well as CD25, and espec ially TCRy8 iIEL, whose function would be most likely to provide protecti on and control inflammation at the intestinal level ( 13). In the present study, we confirm the existence of an inflammatory (29). In the present report we hypothesize that y8+ T cells have been early stimulated since weaning (severe protein deficiency) by the big load of dextrin, favouring a Thl response with production of TNF-a accompanied by an increase in the levels ofTNF-a in the intestinal fluid.…”

Section: Discussionsupporting

confidence: 85%

Cytokines Mediating Inflammation in a Model of Secondary Immunodeficiency in Wistar Rats: Immunomodulation Triggered by Thymomodulin

Olmos¹,

Blois

Frecha³

et al. 2006

Eur J Inflamm

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We have previously demonstrated in a rat model of immunodeficiency, an increase in the number of yo T cells in the gut lamina propria and in the number of CD8aa+, CD25+, y8+ subpopulations of intestinal intraepithelial lymphocytes (iIEL). The increased percentage of CD8aa+ iIEL that express CD25 indicates inflammation. The present study confirms the existence of an inflammatory process in the immunodeficient animals (R21) that is not detectable at the histological level but is characterized by an increase ofthe pro-inflammatory cytokines TNF-a and IFN-y. We have shown a direct relationship between TNF receptor II (TNF-RII) expression and the higher levels of the y8+ iIEL expressing TNFa (TCRy8+/TNF-a+ cells) that could be indicating a differential T cell reactivity. The effects of the increased expression of inflammatory cytokines such as TNF-a and INF-yseem to be down regulated by the high levels of antigen specific TGF-~expression, which, we believe, is antigen specific and appears to maintain oral tolerance. Finally, in malnourished animals NF-KB remains principally in the cytosol and is unable to translocate to the nucleus, indicating the existence of alterations in the metabolic pathways leading to nuclear factor KB translocation from the cytoplasm to the nucleus. The therapeutic action of the immunomodulator TmB was demonstrated by its capacity to return all the cytokines studied to control levels. Moreover, its effects allowed the transcription factor NF-KB to translocate to the nucleus from the cytosol.The gastrointestinal tract is the central organ for the uptake of fluids and nutrients, and at the same time it forms the main protective barrier between the sterile environment ofthe body and the outside world. Intestinal mucosal lymphocytes, including lamina propria and intestinal intraepithelial lymphocytes (iIEL) serve a critical role in the mucosal immune system. The intestinal intraepithelial lymphocytes provide a unique intestinal defense mechanism due to their qualitative and quantitative contributions to the biology of the mucosal immune system. The iIEL constitute an unusual immunological compartment and a heterogeneous population of cells (1-2). Thus, intraepitheliallymphocytes are in sentinel locations to potentially serve as regulatory cells for mucosal immune responses. They have a number of important immunological functions, such as cytotoxic activity, secretion of cytokines and modulation of epithelial cell death and regeneration (3). The intestine of higher vertebrates is a major T

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Section: Discussionsupporting

confidence: 85%

Cytokines Mediating Inflammation in a Model of Secondary Immunodeficiency in Wistar Rats: Immunomodulation Triggered by Thymomodulin

Olmos¹,

Blois

Frecha³

et al. 2006

Eur J Inflamm

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“…1). The majority of the cdT cells in the lungs were of the Vd4-subtype, suggesting intestinal origin [3], while the portion of other cdT cell subpopulations usually found in healthy lungs or lymphoid organs (Vc2Vd5/6 and Vc1.2Vd5/6) was comparatively minor. These observations corresponded with increased HSP72 expression on surface of PMN in the lungs, indicating that HSP72 expression may be related to the protective effects of cdT cells in vivo.…”

Section: Discussionmentioning

confidence: 89%

“…Conventional abT lymphocytes need 5-7 days to manifest their cytotoxic activity [3,5] and thus it is not surprising that self-tolerant clones of circulating abT lymphocytes did not recognize autologous PMN as targets. The cytotoxic activity of cdT cells against activated macrophages plays an important role in the down-regulation of inflammatory reactions [9,10].…”

Section: Discussionmentioning

confidence: 99%

“…T lymphocytes bearing the cd heterodimer of the T cell receptor (cdT cells) have been implicated in the regulation of the host defense against microbial invasion and in the response to inflammation [3][4][5]. The regulatory function of cdT cells is mediated through the production of cytokines such as IFN-c, IL-10, and TNF-a as well as through direct cytotoxicity towards target cells, resulting in the resolution of inflammatory processes [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Surface expression of HSP72 by LPS‐stimulated neutrophils facilitates γδT cell‐mediated killing

Hirsh¹,

Hashiguchi²,

Chen³

et al. 2006

Eur J Immunol

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During inflammation and sepsis, accumulation of activated neutrophils causes lung tissue damage and organ failure. Effective clearance of neutrophils reduces the risk of organ failure; however, its mechanisms are poorly understood. Because lungs are rich in cdT cells, we investigated the physiological role of these cells in the protection of lung tissue from infiltrating neutrophils. In a mouse model of sepsis, we found that the lungs of survivors contained significantly higher numbers of cdT cells than those of mice that died from sepsis. The number of cdT cells correlated inversely with the number of neutrophils in the lungs and with the degree of lung tissue damage. LPS rapidly elicited the expression of heat shock protein (HSP) 72 on the surface of human neutrophils. Inhibitors of transcription, protein synthesis, and intracellular protein transport blocked HSP72 expression, indicating that de novo synthesis is required. cdT cells targeted and rapidly killed LPS-treated neutrophils through direct cell-to-cell contact. Pre-treatment with neutralizing antibodies to HSP72 diminished neutrophil killing. Our data indicate that HSP72 expression on the cell surface predisposes inflamed neutrophils to killing by cdT cells. This intercellular exchange may allow cdT cells to resolve inflammation and limit host tissue damage during sepsis.

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“…Like ␣␤ T cells, they bear a TCR and can be polarized to produce Th1-or Th2-type cytokines (28 -30), but in contrast they are more limited in TCR diversity (27), bear certain innate-like receptors such as NKG2D (31), and have more rapid kinetics of cell proliferation and effector function (L. Liu, personal communication). In addition, they can rapidly produce cytokines in response to microbial Ags (32) and have unique features including a lack of MHC restriction and the capacity to react with Ags without the requirement for undergoing conventional Ag processing, which together suggest a role in early pathogen control (33)(34)(35). Increased numbers of ␥␦ T cells in the peripheral blood and/or localization to sites of infection have been documented in several human viral infections including HIV (36,37), EBV (38,39), and CMV (40).…”

Section: W Est Nile (Wn)mentioning

confidence: 99%

IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection

Wang

Scully

Yin

et al. 2003

The Journal of Immunology

171

187

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West Nile (WN) virus causes fatal meningoencephalitis in laboratory mice, thereby partially mimicking human disease. Using this model, we have demonstrated that mice deficient in γδ T cells are more susceptible to WN virus infection. TCRδ−/− mice have elevated viral loads and greater dissemination of the pathogen to the CNS. In wild-type mice, γδ T cells expanded significantly during WN virus infection, produced IFN-γ in ex vivo assays, and enhanced perforin expression by splenic T cells. Adoptive transfer of γδ T cells to TCRδ−/− mice reduced the susceptibility of these mice to WN virus, and this effect was primarily due to IFN-γ-producing γδ T cells. These data demonstrate a distinct role for γδ T cells in the control of and prevention of mortality from murine WN virus infection.

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Gamma-Delta T Cells: Immunoregulatory Functions and Immunoprotection

Cited by 20 publications

References 197 publications

Cytokines Mediating Inflammation in a Model of Secondary Immunodeficiency in Wistar Rats: Immunomodulation Triggered by Thymomodulin

Cytokines Mediating Inflammation in a Model of Secondary Immunodeficiency in Wistar Rats: Immunomodulation Triggered by Thymomodulin

Surface expression of HSP72 by LPS‐stimulated neutrophils facilitates γδT cell‐mediated killing

IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection

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