γδ T Cells in Host Defense and Epithelial Cell Biology

Boismenu, Richard; Havran, Wendy L.

doi:10.1006/clin.1997.4468

Cited by 66 publications

(46 citation statements)

References 119 publications

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“…D'Souza et al (57) also showed that ␥␦ T cells regulated cellular trafficking of lymphocytes and monocytes into the pleural cavity of Mycobacterium tuberculosis-infected mice, possibly by secretion of specific chemokines. The role of ␥␦ T cells as a source of chemokines has not been well established, but intraepithelial ␥␦ T cells have been shown to express MIP-1␣, MIP-1␤, RANTES, and lymphotactin but not MCP-1 (58). We have obtained similar data in human ␥␦ T cell clones that express the V␦2 TCR (59).…”

Section: Discussionmentioning

confidence: 71%

Experimental Autoimmune Encephalomyelitis on the SJL Mouse: Effect of γδ T Cell Depletion on Chemokine and Chemokine Receptor Expression in the Central Nervous System

Rajan

Asensio

Campbell

et al. 2000

The Journal of Immunology

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Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system (CNS) that is a model for multiple sclerosis. Previously, we showed that depletion of γδ T cells significantly reduced clinical and pathological signs of disease, which was associated with reduced expression of IL-1β, IL-6, TNF-α, and lymphotoxin at disease onset and a more persistent reduction in IFN-γ. In this study, we analyzed the effect of γδ T cell depletion on chemokine and chemokine receptor expression. In the CNS of control EAE mice, mRNAs for RANTES, eotaxin, macrophage-inflammatory protein (MIP)-1α, MIP-1β, MIP-2, inducible protein-10, and monocyte chemoattractant protein-1 were detected at disease onset, increased as disease progressed, and fell as clinical signs improved. In γδ T cell-depleted animals, all of the chemokine mRNAs were reduced at disease onset; but at the height of disease, expression was variable and showed no differences from control animals. mRNA levels then fell in parallel with control EAE mice. ELISA data confirmed reduced expression of MIP-1α and monocyte chemoattractant protein-1 at disease onset in γδ T cell-depleted mice, and total T cell numbers were also reduced. In normal CNS mRNAs for CCR1, CCR3, and CCR5 were observed, and these were elevated in EAE animals. mRNAs for CCR2 were also detected in the CNS of affected mice. Depletion of γδ T cells reduced expression of CCR1 and CCR5 at disease onset only. We conclude that γδ T cells contribute to the development of EAE by promoting an inflammatory environment that serves to accelerate the inflammatory process in the CNS.

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Section: Discussionmentioning

confidence: 71%

Experimental Autoimmune Encephalomyelitis on the SJL Mouse: Effect of γδ T Cell Depletion on Chemokine and Chemokine Receptor Expression in the Central Nervous System

Rajan

Asensio

Campbell

et al. 2000

The Journal of Immunology

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“…19,25,26 In the murine system, distinct subsets of cd T cells bearing specific pairs of the c and d TCR chains are targeted to particular epithelial locations during development such as the skin, lungs, uterus, vagina and tongue where they make up a significant portion of the local intraepithelial lymphocyte population and appear to respond to endogenous stress-induced antigens that have yet to be unambiguously identified. [27][28][29][30][31] For some of these special niche localized cd T…”

Section: Species Specificity: the Best Laid Plans Of Mice And Men Oftmentioning

confidence: 99%

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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“…6 Early secretion of a distinct panel of lymphokines by ␥␦ T cells may be able to enhance the ␣␤ T-cell response elicited by a particular pathogen. 7 Further, not only peripheral ␥␦ T cells exhibited a strong MHC-independent cytotoxic activity against a variety of transformed cells and tumor cells in vitro, but also tumor site-infiltrated ␥␦ T cells were capable of killing autologous tumors. 7,8 These results suggest that ␥␦ T cells may play an early role in host immune surveillance.…”

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confidence: 94%

Peripheral γδ T‐cell deficit in nasopharyngeal carcinoma

Zheng

Chua

et al. 2002

Intl Journal of Cancer

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Previous studies identified CD56؉ and CD56 ؊ subsets of peripheral ␥␦ T cells from healthy donors. Both subsets responded to stimulation by a myeloma cell line, XG-7 and undergo vigorous ex vivo expansion in the presence of exogenous IL-2. They are cytotoxic for different tumor targets including nasopharyngeal carcinoma, but they differ from one another in that the CD56 ؊ subset has an additional growth requirement for IL-7 and exhibited greater cytotoxicity against nasopharyngeal carcinoma (NPC) targets. These immune cells were further shown to retard tumor growth in a nude mice NPC model. To assess if these immune cells might contribute to host defense against NPC, we compared ␥␦ T-cell status of NPC patients with healthy donors and survivors who had been in clinical remission of the cancer. It was found that peripheral ␥␦ T cells of patients were impaired in their response to the stimulatory effects of XG-7 and exhibited weak or essentially no cytotoxicity for the NPC targets. The deficits were present in early and advanced stages of the cancer but were restored among survivors after successful treatment of the cancer. These findings support a role for peripheral ␥␦ T cells in host defense against NPC. It was noted that these immune cells comprise less than 5% of peripheral blood monocytic cells and hence it was not surprising that this component of host defense was breached early in the development of the cancer. © 2002 Wiley-Liss, Inc. Key words: ␥␦ T cells; immune deficit; NPC; tumor immunityT-cell immunity is the principal component of host defense against chronic infection and tumors. The effector arms are mainly composed of 2 subpopulations of cytotoxic T lymphocytes (CTLs) bearing TCR-␣␤ or -␥␦ chains. The ␣␤ CTLs recognize processed antigenic peptides bound to the major histocompatibility complex (MHC) and hence their effector functions are restricted to targets that express identical or related MHC. The ␥␦ T cells effect non-MHC-restricted killing. Although ␥␦ T cells constitute only 1-10% of circulating T cells, recent studies have demonstrated that this minor subpopulation of T cells plays a more important role in the host immune defense than their relatively sparse numbers might suggest. 1,2 These 2 subpopulations of T cells are generally believed to serve a complementary role in host surveillance. However, the ultimate niche of ␥␦ T cells in human immune system is still unclear.A variety of human diseases have been demonstrated to associate with a selective proliferation of blood ␥␦ T cells. It was observed that ␥␦ T-cell numbers increased in patients with tuberculosis 1 (TB) and in healthy individuals in contact with TB patients. 3 In human ehrlichiosis, ␥␦ T cells represented a majority of blood lymphocytes that accounted for as much as 97% of circulating T cells at early stage for about 2 weeks before returning to a normal ␣␤/␥␦ ratio. 4 In the "silent" periods of celiac disease where pathology was mildest, it was found that the number of ␥␦ T cells was higher, suggesting that these cells may ...

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γδ T Cells in Host Defense and Epithelial Cell Biology

Cited by 66 publications

References 119 publications

Experimental Autoimmune Encephalomyelitis on the SJL Mouse: Effect of γδ T Cell Depletion on Chemokine and Chemokine Receptor Expression in the Central Nervous System

Experimental Autoimmune Encephalomyelitis on the SJL Mouse: Effect of γδ T Cell Depletion on Chemokine and Chemokine Receptor Expression in the Central Nervous System

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

Peripheral γδ T‐cell deficit in nasopharyngeal carcinoma

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