The function of γδ T cells in innate immunity

Born, Willi K.; Reardon, Christopher; O’Brien, Rebecca L.

doi:10.1016/j.coi.2005.11.007

Cited by 177 publications

(143 citation statements)

References 57 publications

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“…␥␦ T cells engage in regulatory interactions with macrophages and dendritic cells (26) and play a significant role in macrophage homeostasis. Up-regulation of macrophage cytokine production by ␥␦ T cells during bacterial infection was recently demonstrated (27).…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Imamov

Yakimchuk

Morani

et al. 2007

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

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Interstitial cystitis/painful bladder syndrome is a disease seen mostly in women, and symptoms tend to be worse premenopausally or during ovulation. The four cardinal symptoms of interstitial cystitis/painful bladder syndrome are bladder pain, urgency, frequency, and nocturia. Estrogen has been implicated in the etiology of this disease, but the role of the two estrogen receptors (ER), ER␣ and ER␤, has not been investigated. We found that, in the bladders of WT mice, ER␤ is expressed in the basal cell layer of the urothelium. Bladders of male ER␤ ؊/؊ mice were intact and morphologically indistinguishable from those of their WT littermates. However, in female ER␤ ؊/؊ mice, there was ulceration and atrophy of bladder urothelium concomitant with infiltration of ␥␦ T cells concentrated in the areas of atrophy and shedding of urothelium. The data support the idea that activated ␥␦ T cells are causing the damage to the urothelium. The hyperactivity of T cells may be because of an imbalance between ER␣ and ER␤ signaling in female ER␤ ؊/؊ mice. Our data suggest that reduced ER␤ signaling might have a role in the pathogenesis of interstitial cystitis, and ER␤ could be a candidate for a target of medical therapy.␥␦ T cells ͉ urothelium ͉ painful bladder syndrome T he etiology of interstitial cystitis (IC) is unknown, and available treatment options are limited and mostly palliative. There is a clear role for the immune system in this disease: increased numbers of T lymphocytes, particularly ␥␦ T cells, abnormal urothelial HLA, and overexpression of HLA class II (1) in the urothelium and lamina propria in patients with IC strongly suggest a role for autoimmunity in development of IC (2). Because IC is almost exclusively a disease of young women, and symptoms tend to worsen premenopausally or during ovulation, the role of estrogen receptors (ERs) is likely to be important.The bladder is one of those tissues that were long thought to be nonestrogen-responsive on the basis of the lack of ER␣ expression. The discovery of the second ER, ER␤, provided an explanation for the effects of estrogen in several ER␣-negative tissues such as the prostate, intestine, and lung, where ER␤ serves as a modulator of terminal differentiation of epithelium (3-7). ER␤ and ER␣ knockout mice (ER␤ Ϫ/Ϫ and ER␣ Ϫ/Ϫ ) have been invaluable in analyzing and dissecting the functions of ER␤ and ER␣ (8, 9).The predominant ER in the bladder is ER␤, with very little ER␣ expression (10, 11). Reduced ER␤ expression levels have been reported in the bladders of rats with chemically induced cystitis (12). In the present study, with the use of ER␤ Ϫ/Ϫ mice, we have investigated the role of ER␤ in the bladder urothelium. We report that, in female ER␤ Ϫ/Ϫ but not in ER␣ Ϫ/Ϫ mice, there is autoimmune destruction of urothelium resembling IC. ResultsImmunohistochemical staining of WT mouse bladder sections showed that ER␤ is expressed in bladder urothelium and localized in the basal cell layer (Fig. 1). In the bladders of female ER␤ Ϫ/Ϫ mice, there were specific morphol...

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Section: Discussionmentioning

confidence: 99%

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Imamov

Yakimchuk

Morani

et al. 2007

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

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“…Nonetheless, downstream proliferation is likely, as we have demonstrated in vitro. Increased lymphatic γδ T cells in calves correlated with resistance to Salmonella infection (data not shown), and would contribute to dendritic cell maturation [30], potentially present antigen [31] and may interact with monocytes to resolve inflammation [32].…”

Section: Discussionmentioning

confidence: 99%

Mucosal lymphatic-derived γδ T cells respond early to experimental Salmonella enterocolitis by increasing expression of IL-2Rα

Hedges

Buckner

Rask

et al. 2007

Cellular Immunology

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To better understand the roles of γδ T cells in mucosal infection, we utilized Salmonella enterica serovar Typhimurium (Salmonella serovar Typhimurium) infection in cattle as it closely approximates Salmonella serovar Typhimurium-induced enterocolitis in humans. Protein and gene expression in αβ and γδ T cells derived from lymphatic ducts draining the gut mucosa in Salmonella serovar Typhimurium infected calves were analyzed. In calves with enterocolitis, general gene expression trends in γδ T cells suggested subtle activation and innate response, whereas αβ T cells were relatively quiescent following Salmonella serovar Typhimurium infection. An increase in IL-2Rα expression on γδ T cells from infected calves and results from in vitro assays suggested that γδ T cells were primed by Salmonella serovar Typhimurium LPS to better respond to IL-2 and IL-15. Together with gene expression trends in vivo, these data support early priming activation of target tissue γδ T cells during Salmonella serovar Typhimurium infection.

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“…cd-T cells represent only a minor T-cell population in peripheral blood (2%-10% of CD3 1 T cells), but constitute the major subset of resident T cells in mucosa and skin. 2 This preferential distribution favors their initial in situ anti-infection activities. Compared with the T-cell receptors (TCRs) of conventional ab-T cells, the TCRs of cd-T cells are relatively invariant and the exact ligands they recognize are still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 The roles of cd-T cells are multifaceted and correlate with their distribution and differentiation. 2 On the one hand, epidermal cd-T cells play an indispensable role in limiting and eliminating invasive pathogens and recruiting inflammatory cells to infected locations, 6,7 while skin cd-T cells promote tissue repair by producing keratinocyte growth factor. 8 On the other hand, some cd-T cells, especially IL-17-producing cd-T cells, have been confirmed to be involved in the pathogenesis of transplantation rejection, 9 autoimmune diseases, [10][11][12][13] inflammatory diseases 14,15 and allergy 16 in human and animal models.…”

Section: Introductionmentioning

confidence: 99%

γδ-T cells: an unpolished sword in human anti-infection immunity

et al. 2012

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cd-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of cd-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis. cd-T cells have both 'innate' and 'adaptive' characteristics in the immune response, and their anti-infection activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in cd-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different cd-T cell subpopulations under specific conditions, cd-T cell-based therapy has great potential for the treatment of infectious diseases.

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The function of γδ T cells in innate immunity

Cited by 177 publications

References 57 publications

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Estrogen receptor β-deficient female mice develop a bladder phenotype resembling human interstitial cystitis

Mucosal lymphatic-derived γδ T cells respond early to experimental Salmonella enterocolitis by increasing expression of IL-2Rα

γδ-T cells: an unpolished sword in human anti-infection immunity

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