Integrin αEβ7: Molecular Features and Functional Significance in the Immune System

Hadley, Gregg A.; Higgins, Jonathan M.G.

doi:10.1007/978-94-017-9153-3_7

Cited by 39 publications

(32 citation statements)

References 115 publications

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“…The expression of CD69 and CD103, two proteins thought to enhance retention of T cells in tissue (16, 17), was compared on total CD4+ and CD8+ T cells isolated from PBMC and cervical samples. Representative data (Figure 2A) and summarized data (Figure 2B) show that CD69 was expressed on a higher proportion of CD4+ (medians 81.1% versus 0.8%, P=0.008) and CD8+ T cells (medians 75.7% versus 3.2%, P=0.008) isolated from cervical biopsies versus blood (n=9).…”

Section: Resultsmentioning

confidence: 99%

“…Surface expression of CD69, an early leukocyte cell activation marker, has been shown to interfere with sphingosine-1-phosphate receptor function leading to T cell retention and local memory formation (16). CD103, a constituent of αEβ7 integrin, participates in T cell retention through interaction with E-cadherin expressed on epithelial cells (17). Studies of human organ donors revealed that the highest frequency of CD69 expression was on tissue-derived CD4+ and CD8+ T RM , and that CD103 was most highly expressed by gut-derived CD8+ T cells (21, 25).…”

Section: Discussionmentioning

confidence: 99%

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Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract

et al. 2017

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Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantitate HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T cell responses to HSV-2. Compared to their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7−/CD45RA−) and the majority expressed CD69, a marker of tissue residency. Co-expression of CD103, another marker of tissue residency, was highest on cervix-derived CD8+ T cells. Functional HSV-2 reactive CD4+ and CD8+ T cells responses were detected in cervical samples and a median of 17% co-expressed CD103. HSV-2 reactive CD4+ T cells co-expressed IL-2 and were significantly enriched in the cervix compared to blood. This first direct ex vivo documentation of local enrichment of HSV-2 reactive T cells in the human female genital mucosa is consistent with the presence of antigen-specific tissue-resident memory T cells. Ex vivo analysis of these T cells may uncover tissue-specific mechanisms of local control of HSV-2 to assist the development of vaccine strategies that target protective T cells to sites of HSV-2 infection.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract

et al. 2017

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“…Of note, ltgb7−/ − mice also lacks CD103. However, CD103 mainly plays a role for the retention of T cells in the epithelia whereas α4β7 is responsible for trafficking (39). Our results with ltgb7−/ − mice show that the enhanced local E7-specific CD8+ T cell response by our vaccination approach is mainly mediated by α4β7 (Figure 5).…”

Section: Discussionmentioning

confidence: 99%

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract

Sun

Peng

Liang

et al. 2016

Clinical Cancer Research

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Purpose Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Experimental Design Here we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than IM delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc). Results We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Conclusions Our results support future clinical translation using cervicovaginal TA-HPV vaccination.

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“…It is a known ligand of E-cadherin, a homotypic adhesion molecule expressed by epithelial cells in barrier tissues 58 . In mouse models, CD8 T cells specific for HSV-1 enter the skin lacking CD103 expression, and then in response to epidermal TGFβ upregulate CD103 6 .…”

Section: Common Features Of Trm In Barrier Tissuesmentioning

confidence: 99%

The emerging role of resident memory T cells in protective immunity and inflammatory disease

Park

Kupper

2015

Nat Med

456

449

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Over the past decade, it has become clear that there is an important subset of memory T cells that resides in tissues — tissue resident memory T cells (TRM). There is an emerging understanding that TRM have a role in human tissue specific immune and inflammatory diseases. Furthermore, the nature of the molecular signals that maintain TRM in tissues is the subject of much investigation. In addition while it is logical for TRM to be located in barrier tissues at interfaces with the environment in human and mouse, TRM have also been found in brain, kidney, joint, and other non-barrier tissues in both species. Their biology and behavior make it likely that they play a role in chronic relapsing and remitting diseases of both barrier and non-barrier tissues. This review will discuss recent understandings of the biology of TRM with a particular focus on their role in disease.

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Integrin αEβ7: Molecular Features and Functional Significance in the Immune System

Cited by 39 publications

References 115 publications

Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract

Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell–Mediated Tumor Control in the Genital Tract

The emerging role of resident memory T cells in protective immunity and inflammatory disease

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