Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium

Yeaman, Grant R.; Guyre, Paul M.; Fanger, Michael W.; Collins, Jane; White, Hillary D.; Rathbun, Wayne; Orndorff, Kenneth A.; González, J. Navarro; Stern, Judy E.; Wira, Charles R.

doi:10.1002/jlb.61.4.427

Cited by 178 publications

(167 citation statements)

References 19 publications

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“…CD19 + lymphocytes have previously been located in follicle-like structures in the subepithelial layers of the ectocervical mucosa with immunohistochemical technology (40), supporting our finding of CD19 mRNA in the ectocervix. Endometrial aggregates of CD19 + lymphocytes increase in size during mid-cycle and the secretory phase of the menstrual cycle (41), supporting the finding of hormonal influence on CD19 + cells. We did not observe any correlation between hormonal contraception and immunoglobulin mRNA expression.…”

Section: Discussionsupporting

confidence: 80%

Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women

Wendel

Kaldensjö²,

Peterson³

et al. 2010

Int J Oncol

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Abstract. Persistent human papillomavirus (HPV) infection is a prerequisite for cervical cancer and results from bypassing the local immune response. Twenty-four volunteers underwent an ectocervical biopsy, Pap smear, tests for sexually transmitted infections including HIV and HPV genotyping. All answered a questionnaire regarding medical history. Repeat Pap smear and HPV genotyping was performed 9-26 months later. Quantitative reverse transcriptase (qRT-)PCR was used to assess expression of CD3, CD4, CD8, CD19, CD27, IL-2, IL-12, IL-4, IL-10, IL-17, HLA-DR·, TGFß, IFNÁ, PD-1, PD-L1, CTLA-4, LAG3, IgA, IgG, CCR5, CCL5/RANTES and the IL-7 receptor in the biopsies. Eleven of 24 volunteers were HPV DNA-positive at baseline. Four of 10 were infected with a persistent HPV genotype at followup. All target molecules were successfully amplified and quantified except for IL-4. We found no difference in mRNA expression of these molecules when comparing HPV DNApositive and -negative women, neither when comparing persistently infected individuals or those who cleared the infection. However, mRNA expression of the B cell phenotypic marker CD19 was higher in women using hormonal contraception than those not (p<0.05). HPV infection does not evoke a local inflammatory immune response in the ectocervix measurable with qRT-PCR. Hormonal contraception may influence B cell activity in the cervix.

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Section: Discussionsupporting

confidence: 80%

Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women

Wendel

Kaldensjö²,

Peterson³

et al. 2010

Int J Oncol

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“…IFN-γ is secreted by uterine neutrophil-like cells in the stroma (Yeaman et al, 1998) or from lymphoid aggregates in the basalis (the lower one-third of endometrium, which is not shed at menstruation) (Tabibzadeh, 1994). The uterine lymphoid aggregates appear to be structured with T (CD8 + ) and B cells surrounded by a 'halo' of monocytes and macrophages (Yeaman et al, 1997). These structures, which are predominant at mid-cycle and in the secretory phase, may play an important role in implantation and, as a source of IFN-γ, may stimulate endometrial stromal cell production of monocyte chemotactic protein (MCP-1), IL-6 and granulocyte colony-stimulating factor and reduce production of IL-8 (Nasu et al, 1998).…”

Section: Stromamentioning

confidence: 99%

Cytokine control in human endometrium

Kelly

King²,

Critchley³

2001

Reproduction

210

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Critical reproductive events in endometrium such as menstruation and implantation have an inflammatory character (Finn, 1986). Menstruation and implantation involve both prostaglandins and cytokines and are accompanied by the ingress of leucocytes into the endometrium. Moreover, oedema is characteristic of endometrium both premenstrually and at the time of implantation. Endometrial physiology relating to these events is still poorly understood and this ignorance hinders better medical approaches to major pathologies of menstruation, such as menorrhagia and dysmenorrhoea, and failure of implantation.One of the most revealing studies on the mechanism of menstruation was published 60 years ago by Markee (1940) who transplanted endometrium to the anterior chamber of the monkey eye, where events surrounding menstruation could be observed microscopically. The early events of menstruation involve vasoconstriction of the spiral blood vessels followed by a relaxation of the arterioles and reperfusion of the tissue. Prolonged periods of vasoconstriction that would have induced hypoxia and the inevitable reperfusion injury were also observed. Such periods of vasoconstriction have not been confirmed in women in studies with techniques such as Doppler flow (Gannon et al., 1997) and xenon clearance (Fraser et al., 1987), but such techniques are unlikely to detect highly localized changes. Hypoxia would certainly be a sufficient cause of cytokine release since hypoxia affects the NFκB pathway (Royds et al., 1998) and many genes have hypoxic response elements. Re-exposure to oxygen is likely to be accompanied by an upregulation of cytokine (Karakurum et al., 1994) matrix metalloproteinase (MMP) (Fujimura et al., 1999; Heo et al., 1999) vascular endothelial growth factor (VEGF) (Goldberg and Schneider, 1994;Sharkey et al., 2000) and prostaglandin (Kishimoto et al., 1997) production. However, the events preceding vasoconstriction are less clear. The early events in menstruation are initiated by the withdrawal of the circulating progesterone as a result of the demise of the corpus luteum and are likely to involve cells close to the spiral arterioles where the constriction Cytokines within endometrium participate in both menstruation and implantation but also contribute to the defence mechanisms of the mucosal epithelium. Endometrium is under the control of steroid hormones, particularly progesterone and, thus, control of cytokines by this steroid is important. Although appreciable numbers of progesterone receptors are not found in endometrial leucocytes, progesterone can modulate cytokines by acting on uterine cells expressing the receptor. The NFκB pathway is important in the control of cytokine synthesis and can modulate production of chemokines, matrix metalloproteinases and the inducible prostaglandin synthesis enzyme COX-2. NFκB activity can be inhibited by progesterone by either stimulating synthesis of IκB, the molecule that restrains NFκB in the cytosol, or after binding to the nuclear receptor, competing with NFκB for ...

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“…In the FRT, more than 95% of T cells are effector memory (Saba et al., 2010; Yeaman et al., 1997), with a high proportion of T cells expressing CD103 in the vagina, endocervix (CX), ectocervix (ECX), and endometrium (EM) (Duluc et al., 2013; Moylan et al., 2016; Rodriguez‐Garcia et al., 2017). Along with resident T cells, mucosal surfaces are populated by multiple subsets of resident DCs critical for the induction and maintenance of T‐cell responses (Schlitzer, McGovern & Ginhoux, 2015).…”

Section: Introductionmentioning

confidence: 99%

Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

et al. 2018

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SummaryAs women age, susceptibility to systemic and genital infections increases. Tissue‐resident memory T cells (TRMs) are CD103+ CD8+ long‐lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8+ T cells. While CD103+ CD8+ T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103+ CD8+ T cells were increased in postmenopausal compared to premenopausal women. Endometrial DCs from postmenopausal women were significantly more effective at inducing CD103 expression on allogeneic naïve CD8+ T cells than DCs from premenopausal women; CD103 upregulation was mediated through membrane‐bound TGFβ signaling. In contrast, cervical CD103+ T cells and DC numbers declined in postmenopausal women with age. Decreases in DCs correlated with decreased CD103+ T cells in endocervix, but not ectocervix. Our findings demonstrate a previously unrecognized compartmentalization of TRMs in the FRT of postmenopausal women, with loss of TRMs and DCs in the cervix with aging, and increased TRMs and DC induction capacity in the endometrium. These findings are relevant to understanding immune protection in the FRT and to the design of vaccines for women of all ages.

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Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium

Abstract: .

Cited by 178 publications

References 19 publications

Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women

Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women

Cytokine control in human endometrium

Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

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Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium

Abstract: .

Cited by 178 publications

References 19 publications

Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women

Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women

Cytokine control in human endometrium

Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract

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Product

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Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract