Tissue-resident T cells lose their S1P1 exit visas

Zajac, Allan; Harrington, Laurie E.

doi:10.1038/cmi.2014.7

Cited by 10 publications

(12 citation statements)

References 18 publications

(19 reference statements)

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“…Unlike the experimental method in Skon et al which evaluates S1P1 mRNA expression through qPCR at least 4 weeks after treatment, we assess S1P1 protein level in just one week after the last vaccination by flow cytometry. The expression of S1P1 changes based on different location and phases of T cells activation and differentiation (38). S1P1 expression is high while the T cells are still in circulation, and as they traffic into the local tissue environment, cytokines milieu triggers the downregulation of S1P1 in T cells leading to their retention in the local environment and gradual differentiation into S1P1-Low Trms.…”

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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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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“…We found that a larger proportion of virus-specific CD8 + T cells in muscle tissue of LysMcre;Arg1 F/F mice were CD69 + at 10 dpi, suggesting that a greater number of T cells are restimulated in the muscle tissue of Arg1-deficient but not Arg1-sufficient mice, augmenting their activation and antiviral functions (e.g., IFN-γ production). Additionally, Cd69 −/− T cells are not efficiently retained in lymphoid tissues and also fail to establish or sustain tissue residency [ 57 , 58 ]. Thus, arginase activity may inhibit virus-specific T cell retention in musculoskeletal tissues, resulting in reduced viral control.…”

Section: Discussionmentioning

confidence: 99%

Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells

et al. 2015

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Arthritogenic alphaviruses, including Ross River virus (RRV) and chikungunya virus (CHIKV), are responsible for explosive epidemics involving millions of cases. These mosquito-transmitted viruses cause inflammation and injury in skeletal muscle and joint tissues that results in debilitating pain. We previously showed that arginase 1 (Arg1) was highly expressed in myeloid cells in the infected and inflamed musculoskeletal tissues of RRV- and CHIKV-infected mice, and specific deletion of Arg1 from myeloid cells resulted in enhanced viral control. Here, we show that Arg1, along with other genes associated with suppressive myeloid cells, is induced in PBMCs isolated from CHIKV-infected patients during the acute phase as well as the chronic phase, and that high Arg1 expression levels were associated with high viral loads and disease severity. Depletion of both CD4 and CD8 T cells from RRV-infected Arg1-deficient mice restored viral loads to levels detected in T cell-depleted wild-type mice. Moreover, Arg1-expressing myeloid cells inhibited virus-specific T cells in the inflamed and infected musculoskeletal tissues, but not lymphoid tissues, following RRV infection in mice, including suppression of interferon-γ and CD69 expression. Collectively, these data enhance our understanding of the immune response following arthritogenic alphavirus infection and suggest that immunosuppressive myeloid cells may contribute to the duration or severity of these debilitating infections.

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“…CD8 + T cells are typically excluded from B cell follicles, since most lack expression of CXCR5, which directs germinal center homing. Fingolimod (FTY720), a drug approved by the US Food and Drug Administration (FDA) for treatment of multiple sclerosis, blocks T cell egress from LN by preventing interaction of sphingosine-1-phosphate (S1P) with four of its receptors (S1PR1, 3, 4, and 5), essentially depriving the T cells of lymph node "exit visas" [66]. As mentioned previously, transcriptional downregulation of S1PR1 is required for establishment of CD8 + T RM [67].…”

Section: A Novel Approach To Hiv Reservoir Eradicationmentioning

confidence: 99%

Defining T Cell Tissue Residency in Humans: Implications for HIV Pathogenesis and Vaccine Design

2020

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Purpose of Review This review summarizes recent literature defining tissue-resident memory T cells (T RM) and discusses implications for HIV pathogenesis, vaccines, and eradication efforts. Recent Findings Investigations using animal models and human tissues have identified a T RM transcriptional profile and elucidated signals within the tissue microenvironment leading to T RM development and maintenance. T RM are major contributors to host response in infectious diseases and cancer; in addition, T RM contribute to pathogenic inflammation in a variety of settings. Although T RM are daunting to study in HIV infection, recent work has helped define their molecular signatures and effector functions and tested strategies for their mobilization. Summary Exclusive reliance on blood sampling to gain an understanding of host immunity overlooks the contribution of T RM , which differ in significant ways from their counterparts in circulation. It is hoped that greater understanding of these cells will lead to novel approaches to prevent and/or eradicate HIV infection.

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Tissue-resident T cells lose their S1P1 exit visas

Cited by 10 publications

References 18 publications

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

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

Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells

Defining T Cell Tissue Residency in Humans: Implications for HIV Pathogenesis and Vaccine Design

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