Tissue instruction for migration and retention of TRM cells

Iijima, Norifumi; Iwasaki, Akiko

doi:10.1016/j.it.2015.07.002

Cited by 88 publications

(83 citation statements)

References 76 publications

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“…The expression of CCR7 on human CD4 T cells in the lower FGT is distinct from characterization studies using human hysterectomy tissue (36) as well as previous studies in mice (14). To better characterize FGT CD4 T cells enriched from the mucosal surface, we measured expression of the tissue retention markers CD69 and CD103 in comparison to CCR7 expression (Figure 2A–C).…”

Section: Resultsmentioning

confidence: 59%

“…Immune-restricted tissues primarily contain memory T cells of an effector memory phenotype (T EM ; CCR7 lo , CD45RA lo ), which recent studies have shown are mostly comprised of long-lived, non-circulating tissue-resident memory cells (T RM : CD103 + CD69 + ) that provide tissue-specific protection from invading pathogens (11, 12). In murine models, resident populations of CD4 T cells in the FGT predominantly comprise a T EM phenotype expressing CD69 but with little to no CD103 expression in comparison to FGT CD8 T RM (13, 14). Interestingly, the protective functions of T RM cells at mucosal sites can be mediated by cells embedded in the tissue as well as cells located on the luminal side of the epithelium (15–18).…”

Section: Introductionmentioning

confidence: 99%

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Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential

Swaims-Kohlmeier

Haaland

Haddad

et al. 2016

The Journal of Immunology

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The female genital tract (FGT) provides a means of entry to pathogens, including HIV, yet immune cell populations at this barrier between host and environment are not well defined. We initiated a study of healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched peripheral blood to investigate potential mechanisms of HIV sexual transmission. Surprisingly, we observed FGT CD4 T cell populations were primarily CCR7hi, consistent with a central memory (TCM) or recirculating memory T cell phenotype. In addition, roughly half of these CCR7hi CD4 T cells expressed CD69, consistent with resident memory T cells (TRM), while the remaining CCR7hi CD4 T cells lacked CD69 expression, consistent with recirculating memory CD4 T cells that traffic between peripheral tissues and lymphoid sites. HIV susceptibility markers CCR5 and CD38 were increased on FGT CCR7hi CD4 T cells compared to blood, yet migration to the lymphoid homing chemokines CCL19 and CCL21 was maintained. Infection with GFP-HIV showed that FGT CCR7hi memory CD4 T cells are susceptible HIV targets, and productive infection of CCR7hi memory T cells did not alter chemotaxis to CCL19 and CCL21. Variations of resident CCR7hi FGT CD4 T cell populations were detected during the luteal phase of the menstrual cycle and longitudinal analysis showed the frequency of this population positively correlated to progesterone levels. These data provide evidence women may acquire HIV through local infection of migratory CCR7hi CD4 T cells and progesterone levels predict opportunities for HIV to access these novel target cells.

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Section: Resultsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential

Swaims-Kohlmeier

Haaland

Haddad

et al. 2016

The Journal of Immunology

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“…CD8-Trm are known to rapidly produce IFNγ upon stimulation4, and we hypothesised that the low expression levels of CD8 and CD69 would result in a lower capacity to produce IFNγ as the change infers a regulatory phenotype2627. We stimulated endometrial T cells with CD3/CD28-beads and analysed their potential to produce IFNγ by intracellular staining and flow cytometry (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Recent murine studies have led to a new understanding of memory CD8-T cells in tissues. The majority of these cells have been characterized as ‘Tissue Resident Memory’ (Trm) cells, which provide the typical rapid effector responses associated with memory cells4, but crucially they do not recirculate. They are therefore independent of lymphoid and peripheral blood memory T cell populations5.…”

mentioning

confidence: 99%

An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage

Southcombe

Mounce

McGee

et al. 2017

Sci Rep

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When trying to conceive 1% of couples have recurrent miscarriages, defined as three or more consecutive pregnancy losses. This is not accounted for by the known incidence of chromosomal aneuploidy in miscarriage, and it has been suggested that there is an immunological aetiology. The endometrial mucosa is populated by a variety of immune cells which in addition to providing host pathogen immunity must facilitate pregnancy. Here we characterise the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress. We demonstrate that unexplained recurrent miscarriage is associated with significantly decreased expression of the T-cell co-receptor CD8 and tissue residency marker CD69. These cells differ from those found in control women, with less expression of CD127 indicating a lack of homeostatic cell control through IL-7 signalling. Nevertheless this population is resident in the endometrium of women who have RM, more than three months after the last miscarriage, indicating that the memory CD8-T cell population is altered in RM patients. This is the first evidence of a differing pre-pregnancy phenotype in endometrial immune cells in RM.

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“…TRM are retained at a site of infection after pathogen clearance and guard against re-infection, and different subsets sit in different anatomical locations within tissues – many CD8 TRM lodge in epithelial layers, and both CD8 and CD4 TRM reside in non-epithelial locations, often in organized memory lymphocyte clusters [47–49]. One hallmark of TRM in many tissues is the transcriptional loss of S1pr1 and surface expression of CD69 [50–53].…”

Section: S1p Signaling and T Cell Exit From Non-lymphoid Organsmentioning

confidence: 99%

Exit Strategies: S1P Signaling and T Cell Migration

Baeyens

Fang

Chen

et al. 2015

Trends in Immunology

126

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Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well-understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies towards measuring S1P.

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Tissue instruction for migration and retention of TRM cells

Cited by 88 publications

References 76 publications

Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential

Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential

An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage

Exit Strategies: S1P Signaling and T Cell Migration

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