A pro-inflammatory CD8+ T-cell subset patrols the cervicovaginal tract

Pattacini, Laura; Davis, Amanda Woodward; Czartoski, Julie; Mair, Florian; Presnell, Scott; Hughes, Sean M.; Hyrien, Ollivier; Lentz, Gretchen M.; Kirby, Anna C.; Fialkow, Michael; Hladik, Florian; Prlic, Martin; Lund, Jennifer M.

doi:10.1038/s41385-019-0186-9

Cited by 14 publications

(33 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently reported that memory CD8 T cells in the human CVT displayed unique phenotypical and functional features including the presence of a subset of CD69 − CD103 − inflammatory CD8 T cells (1). Importantly, the majority of memory CD8 T cells in the CVT of healthy women typically expressed CD103 and CD69, which are biomarkers associated with tissue-residence (2–4), suggesting that most memory CD8 T cells in the human CVT stably reside there.…”

Section: Introductionmentioning

confidence: 99%

Cervicovaginal tissue residence imprints a distinct differentiation program upon memory CD8 T cells

Davé¹,

Cardozo-Ojeda

Mair³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

26The memory CD8 T cell compartment in human cervicovaginal tissue (CVT) is phenotypically 27 and functionally distinct compared to other non-lymphoid tissues. To determine if these 28 distinctive features are driven by residence in the tissue itself, rather than a consequence of 29 local antigenic insults, we used a mouse model to assess memory CD8 T cell differentiation in 30 the CVT. Following systemic immunization to elicit a CD8 T cell response to a herpes simplex 31 virus (HSV) epitope, HSV-specific memory CD8 T cells were stably maintained in other tissues 32 but gradually declined in the CVT over 5 months post-immunization, correlating with a delay in 33 viral control upon HSV challenge. While memory cells in the periphery and small intestine 34 maintained a fairly stable phenotype after 30 days, memory CD8 T cells in the CVT gradually 35 acquired a CD103 + , TCF-1 -, granzyme B + phenotype over the 5 month time span. Notably, a 36 sizable and phenotypically similar population of CD8 T cells was also found in human CVT. Our 37 data indicate that the CVT environment itself considerably affects memory CD8 T cell 38 maintenance and differentiation, and call for a reassessment of the prevalent model of memory 39 T cell maintenance which does not currently account for tissue-specific divergence. 40Pathogens that infect mucosal barrier surfaces represent a significant global health 43 burden, yet immune cell function within reproductive mucosal tissues remains understudied. In 44 addition, the phenotypic and functional characteristics of memory T cells in cervicovaginal tissue 45 (CVT) compared to other mucosal and lymphoid organs is poorly understood, despite the 46 potentially broad importance of this cellular population in the context of sexually-transmitted 47 infections. 48We recently reported that memory CD8 T cells in the human CVT displayed unique 49 phenotypical and functional features including the presence of a subset of CD69 -CD103 -50 inflammatory CD8 T cells (1). Importantly, the majority of memory CD8 T cells in the CVT of 51 healthy women typically expressed CD103 and CD69, which are biomarkers associated with 52 tissue-residence (2-4), suggesting that most memory CD8 T cells in the human CVT stably 53 reside there. Tissue-residence itself can affect functional and phenotypical properties of T cells 54 (5)(6)(7)(8)(9)(10)(11)(12)(13), which is thought to be a consequence of exposure to metabolites, cytokines, and other 55 factors present in the tissue environment in steady state conditions(14, 15) (16). However, it is 56 unclear if the distinctive features of memory CD8 T cells in the CVT are a consequence of 57 recurring local infections and antigenic insults or driven by residence in the tissue itself. To 58 address this question, we used a mouse model system to assess memory CD8 T cell 59 differentiation and maintenance in the CVT. Specifically, we used a systemic immunization 60 strategy to induce HSV-specific memory CD8 T cells. We then tracked these antigen-specific T 61 cells across tissu...

show abstract

Section: Introductionmentioning

confidence: 99%

Cervicovaginal tissue residence imprints a distinct differentiation program upon memory CD8 T cells

Davé¹,

Cardozo-Ojeda

Mair³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Within the T cell compartment, a near 1:1 CD4/CD8 T cell ratio was observed in healthy endometrial biopsies at the secretory phase of the menstrual cycle [54][55][56]. This distribution substantially differs from that of blood (in which CD4 T cells are more frequent) and mirrors that of other barrier tissues that are largely populated by Trm cells, including the endocervix, ectocervix, and vagina [45,57,58]. Indeed, endometrial memory T cells (defined by CD45RO positivity) expressed CD69 (and to a lesser extent, CD8 T cells coexpressed CD103) [54] suggesting that Trm cells are present at the window of implantation.…”

Section: Tissue Residency: Preimplantationmentioning

confidence: 93%

“…While most Trm cells have a Tem-like phenotype, those with Temra phenotypes can also contribute to tissue residence [ 58 ], yet do not express CD45RO, potentially explaining the reported CD69 expression in CD45RO − endometrial T cells [ 54 ]. In line with bona fide tissue residence, CD69 + memory T cells isolated from the endometrium express the proteins PD-1 [ 54 ] or CCR5 [ 55 ] and transcripts for CD49a [ 59 ], mirroring phenotypic and transcriptional signatures broadly shared by human Trm cells across mucosal and lymphoid tissues [ 45 , 49 , 57 ]. While CCR5 expression has long been associated with a Th1 phenotype [ 60 ], a recent study demonstrated that CCR5 + CD4 T cells in healthy and inflamed human barrier tissue are actually potent IL-17 producers [ 45 ].…”

Section: The Memory T Cell Compartment Changes During the Course Omentioning

confidence: 99%

“…In the early stages of pregnancy, in which trophoblast invasion is shallow, a major subset of Tem cells express CD69 (with a lesser fraction of coexpressing CD103 within CD8 T cells) [ 66 ]. While CD103 coexpression in CD69 + CD8 T cells in the first-trimester decidua is markedly less than what is observed in other mucosal tissues [ 45 , 57 , 58 ], it suggests that some degree of TGF-β signaling [ 67 ] may occur at the maternal–fetal interface [ 68 ]. Although these studies detected a large fraction of CD69-expressing T cells (approximately 75% of CD8s and 50% of CD4s) within the decidua, sizable populations of Tcm and naïve T cells were also detected, indicating the presence of (contaminating) blood ( Figure 1 C) and possibly even underestimated frequencies of Trm cells [ 66 ].…”

Section: The Memory T Cell Compartment Changes During the Course Omentioning

confidence: 99%

See 1 more Smart Citation

Human Tissue-Resident Memory T Cells in the Maternal–Fetal Interface. Lost Soldiers or Special Forces?

DeJong

Maurice

McCartney

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

The immune system plays a critical role during pregnancy, but the specific mechanisms and immune cell function needed to support pregnancy remain incompletely understood. Despite decades of research efforts, it is still unclear how the immune system maintains tolerance of fetal-derived tissues, which include most cells of the placenta and of course the fetus itself, without forfeiting the ability to protect against harmful infections. T cells recognize antigen in the context of major histocompatibility complex (MHC) encoded proteins, but classical MHC class I and II expression are diminished in fetal-derived cells. Can T cells present at the maternal–fetal interface (MFI) protect these cells from infection? Here we review what is known in regard to tissue-resident memory T (Trm) cells at the MFI. We mainly focus on how Trm cells can contribute to protection in the context of the unique features of the MFI, such as limited MHC expression as well as the temporary nature of the MFI, that are not found in other tissues.

show abstract

“…CD69 + CD103 − CD8 + Trm cells are also present in the stroma of various tissues, such as the skin, gut, FRT, salivary gland, and brain (Wakim et al 2010;Bergsbaken and Bevan 2015;Smith et al 2015;Thom et al 2015;Watanabe et al 2015;Pattacini et al 2019). A CD103 − CD8 + Trm cell population has also been described in the brain (Wakim et al 2010).…”

Section: Stromal Cd8 + Trm Cell Subpopulationsmentioning

confidence: 99%

Divergence of Tissue-Memory T Cells: Distribution and Function-Based Classification

Takamura

2020

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

Tissue-resident memory T cells (Trm) comprise the majority of memory cells in nonlymphoid tissues and play a predominant role in immunity at barrier surfaces. A better understanding of Trm cell maintenance and function is essential for the development of vaccines that confer frontline protection. However, it is currently challenging to precisely distinguish Trm cells from other T cells, and this has led to confusion in the literature. Here we highlight gaps in our understanding of tissue memory and discuss recent advances in the classification of Trm cell subsets based on their distribution and functional characteristics.

show abstract

A pro-inflammatory CD8+ T-cell subset patrols the cervicovaginal tract

Cited by 14 publications

References 55 publications

Cervicovaginal tissue residence imprints a distinct differentiation program upon memory CD8 T cells

Cervicovaginal tissue residence imprints a distinct differentiation program upon memory CD8 T cells

Human Tissue-Resident Memory T Cells in the Maternal–Fetal Interface. Lost Soldiers or Special Forces?

Divergence of Tissue-Memory T Cells: Distribution and Function-Based Classification

Contact Info

Product

Resources

About