Homing of a γδ thymocyte subset with homogeneous T-cell receptors to mucosal epithelia

Itohara, Shigeyoshi; Farr, Andrew G.; Lafaille, Juan J.; Bonneville, Marc; Takagaki, Yohtaroh; Haas, Werner; Tonegawa, Susumu

doi:10.1038/343754a0

Cited by 498 publications

(357 citation statements)

References 18 publications

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“…found in mucosal epithelial sites such as tongue (30), female reproductive tract (31,32), and resident pulmonary lymphocytes (33). In distinction from V␥5/V␦1 ␥␦ cells, V␥4/V␦1 ␥␦ T cells localize in nonontogenic organs (34).…”

Section: Discussionmentioning

confidence: 99%

Infiltration of Canonical Vγ4/Vδ1 γδ T Cells in an Adriamycin-Induced Progressive Renal Failure Model

Ando

Watson

et al. 2001

The Journal of Immunology

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We have previously reported an infiltration of renal interstitial γδ T cells in Adriamycin-induced progressive glomerulosclerosis in the rat kidney. The TCR repertoire and sequences used by these γδ T cells have now been studied. Two injections of Adriamycin 14 days apart caused segmental glomerulosclerosis, massive interstitial infiltration of mononuclear cells, and end-stage renal failure. Flow cytometry of lymphocyte subpopulations with Abs to CD3, the γδ TCR, and the αβ TCR showed that γδ T cells as a proportion of CD3+ cells were increased in Adriamycin-treated kidneys (8.5 ± 5.4%), but not in lymph nodes (1.3 ± 0.4%). A semiquantitative score of glomerular damage (r = 0.65; p < 0.01) and creatinine (r = 0.62; p < 0.01) correlated significantly with the presence of γδ T cells. TCR Vγ repertoire analysis by RT-PCR and Southern blotting showed that Vγ2 was the dominant subfamily in lymph nodes, whereas Vγ4 became the predominant subfamily in advanced stages of the rat Adriamycin-treated kidney. Sequencing of the Vγ4-Jγ junctional region showed an invariant sequence. The amino acid sequence of the junctional region of the Vγ4 TCR was the same as the reported mouse canonical Vγ4 TCR sequence. Analysis of the kidney Vδ repertoire showed dominant expression of Vδ1, and sequencing again revealed the selective expression of a canonical Vδ1 gene. Semiquantitative RT-PCR for cytokine gene expression showed that γδ T cells from the kidneys expressed TGF-β, but not IL-4, IL-10, or IFN-γ. These results suggest that the predominant γδ T cells in the Adriamycin kidney use an invariant Vγ4/Vδ1 receptor.

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Section: Discussionmentioning

confidence: 99%

Infiltration of Canonical Vγ4/Vδ1 γδ T Cells in an Adriamycin-Induced Progressive Renal Failure Model

Ando

Watson

et al. 2001

The Journal of Immunology

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“…In WT mice, the profile of TCR-V␥ expression was similar to that on day 2 after infection, although TCR-V␥7 mRNA was no longer detected. By contrast, in V␥1 Ϫ/Ϫ mice, TCR-V␥5 and -V␥6 mRNA were detected in addition to TCR-V␥7 mRNA, which was unexpected because V␥5 and V␥6 expressions normally define monomorphic, oligoclonal populations restricted to the skin (V␥5 ϩ dendritic epidermal T cells (DETC)) (43) and mucosal epithelia of the reproductive tract (V␥6) (44). There were also differences in TCR-V␦ expression during the late stage of the response to Lm infection.…”

Section: ␥␦ T Cell Recruitment During Lm Infection Is Regulated By V␥mentioning

confidence: 93%

Delineation of the Function of a Major γδ T Cell Subset during Infection

Andrew

Newton

Dalton

et al. 2005

The Journal of Immunology

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γδ T cells play important but poorly defined roles in pathogen-induced immune responses and in preventing chronic inflammation and pathology. A major obstacle to defining their function is establishing the degree of functional redundancy and heterogeneity among γδ T cells. Using mice deficient in Vγ1+ T cells which are a major component of the γδ T cell response to microbial infection, a specific immunoregulatory role for Vγ1+ T cells in macrophage and γδ T cell homeostasis during infection has been established. By contrast, Vγ1+ T cells play no significant role in pathogen containment or eradication and cannot protect mice from immune-mediated pathology. Pathogen-elicited Vγ1+ T cells also display different functional characteristics at different stages of the host response to infection that involves unique and different populations of Vγ1+ T cells. These findings, therefore, identify distinct and nonoverlapping roles for γδ T cell subsets in infection and establish the complexity and adaptability of a single population of γδ T cells in the host response to infection that is not predetermined, but is, instead, shaped by environmental factors.

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“…1). V γ 6 + γδ T cells express the invariant V γ 6/V δ 1 TCR, develop only in the late embryonic thymus and preferentially localize to the uterus, vagina, lung, dermis and peritoneal cavity 35, 36. On the other hand, V γ 4 + γδ T cells develop in both fetal and adult thymus, have more diverse TCR repertoire and reside in the dermis, lung, liver and secondary lymphoid organs 37, 38.…”

Section: γδ T‐cell Subsets and Their Developmentmentioning

confidence: 99%

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Akitsu

Iwakura

2018

Immunology

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SummaryInterleukin‐17 (IL‐17) is a pro‐inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL‐17‐producing γδ T cells (γδ17 cells) in addition to IL‐17‐producing CD4+ T cells [T helper type 17 (Th17) cells] are often the main producers of IL‐17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra‐thymic differentiation. γδ thymocytes capable of producing IL‐17, which express the transcription factor retinoic‐acid‐receptor‐related orphan receptor γt and the signature cytokine receptor IL‐23R, leave the thymus, and produce IL‐17 rapidly by the stimulation with IL‐1β and IL‐23 in the periphery. Therefore, γδ17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. γδ T cells that can produce IL‐17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL‐17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of γδ17 cells in infection and inflammatory diseases and therapeutic advances targeting IL‐17.

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Homing of a γδ thymocyte subset with homogeneous T-cell receptors to mucosal epithelia

Cited by 498 publications

References 18 publications

Infiltration of Canonical Vγ4/Vδ1 γδ T Cells in an Adriamycin-Induced Progressive Renal Failure Model

Infiltration of Canonical Vγ4/Vδ1 γδ T Cells in an Adriamycin-Induced Progressive Renal Failure Model

Delineation of the Function of a Major γδ T Cell Subset during Infection

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

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