Lymphoid tissue in the endometrium of women with unexplained infertility: morphometric and immunohistochemical aspects

Klentzeris, Lucas D.; Bulmer, Judith N.; Warren, M.A.; Morrison, Lynn; Li, Tin‐Chiu; Cooke, I. D.

doi:10.1093/oxfordjournals.humrep.a138564

Cited by 74 publications

(45 citation statements)

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“…In normal eutopic endometrium, during the proliferative phase, few, if any, CD3-positive T cells were observed which supports previous reports [1,25]. However, we observed increasing numbers of T cells as the menstrual cycle progressed, supporting the concept that the prolifer ative activity of lymphoid cells within the endometrium increases during the secretory phase [26].…”

Section: Discussionsupporting

confidence: 91%

Localization of T Cells, Interferon-Gamma and HLA-DR in Eutopic and Ectopic Human Endometrium

Chiang

Hill

1997

Gynecol Obstet Invest

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Objectives: Immunologic mechanisms are implicated in the pathogenesis of endometriosis and endometriosis-associated reproductive failure. The purpose of this study was to describe key immune response elements in eutopic and ectopic endometrium and to test the hypothesis that expression of CD3-positive T cells, the T-helper 1-type cytokine, IFN-g, and the antigen presentation marker, HLA-DR, vary throughout the menstrual cycle in eutopic endometrium and are more abundantly expressed in ectopic than in eutopic endometrium. Methods: Eutopic and ectopic endometrium obtained at hysterectomy from 7 women with endometriosis were compared with hysterectomy specimens from 7 women with adenomyosis and 10 women without endometriosis or endometrial pathology. Tissues were formalin-fixed, paraffin-embedded, sectioned and stained using the biotin-streptavidin-alkaline phosphatase technique and antibodies to human CD3, IFN-g, and HLA-DR. Eutopic endometrial samples were histologically divided into menses (n = 5), proliferative (n = 9), and secretory (n = 10) phases. Positive control tissues (spleen) and negative controls (no primary antibody) were used in each experiment. Results: T cells, IFN-g and HLA-DR-positive cells were observed in eutopic endometrial samples throughout the menstrual cycle. Glandular epithelium was CD3-negative except for CD3-positive cells surrounding and occasionally interdigitating between glandular epithelium. Glandular epithelium was IFN-g-positive and HLA-DR-positive in all phases except the proliferative phase. Staining was more often observed in the basalis than in the functionalis layer, ranging from patchy staining to the entire gland. T cells, IFN-g, and HLA-DR-positive stromal cells were more abundant in secretory endometrium than in proliferative samples. CD3, IFN-g, and HLA-DR-positive cells were scattered throughout the myometrium and concentrated in vessels. Higher intensity staining was observed in ectopic than in eutopic endometrium, with CD3 and HLA-DR-positive cells forming aggregates around IFN-g and HLA-DR-positive glands. The intensity of IFN-g staining in ectopic endometrium was similar to the intensity of staining observed in menstrual and late secretory basalis samples from eutopic endometrium. Conclusions: The results of this observational study suggest that activated T cells, IFN-g and upregulation of antigen presentation may play a role in normal endometrial physiology. The increased number of T cells, expression of IFN-g and enhanced antigen presentation in ectopic compared to eutopic endometrium support the concept that cellular immune activation is involved in endometriosis and its sequelae.

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Section: Discussionsupporting

confidence: 91%

Localization of T Cells, Interferon-Gamma and HLA-DR in Eutopic and Ectopic Human Endometrium

Chiang

Hill

1997

Gynecol Obstet Invest

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“…That endometrial leucocytes play a role in fertility is suggested by immunohistochemical studies documenting a reduction in CD8+ T cells and an increase in CD4+ T cells throughout the luteal phase in endometrium from women with unexplained infertility. 28 Further studies of the regulation of endometrial immune cell populations should examine regulation of both cell numbers and function by soluble factors produced by endothelial stromal and epithelial cells in response to altered steroid hormone levels.…”

Section: Discussionmentioning

confidence: 99%

Endometrial leucocytes: expression of steroid hormone receptors.

1998

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Background-Stromal leucocyte populations in human endometrium comprise T cells, macrophages, and phenotypically unusual endometrial granulated lymphocytes. Their proportions vary during the menstrual cycle and, in particular, endometrial granulated lymphocytes increase in number in the late secretory phase. The stimulus responsible for these cyclical changes is unknown but it is likely that the steroid hormones oestrogen and progesterone play a role. Aims-To define further the expression of steroid hormone receptors by leucocytes in non-pregnant and pregnant human endometrium. Methods-Frozen and paraYn wax embedded sections of endometrium from non-pregnant women and early pregnancy decidua were labelled using single and double immunohistochemical techniques with monoclonal antibodies directed against oestrogen and progesterone receptors and various leucocyte subpopulations. Results-Despite the prominence of CD56 positive endometrial granulated lymphocytes in late secretory phase endometrium and early pregnancy decidua, double immunohistochemical labelling showed no evidence of expression of either progesterone or oestrogen receptors by these cells or other endometrial leucocyte populations. Conclusions-Rather than acting directly, steroid hormones are likely to influence endometrial leucocyte populations indirectly via products of endometrial stromal or epithelial cells that express steroid hormone receptors. (J Clin Pathol 1998;51:121-126)

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“…There have been several reports of perturbation of the normal CD8:CD4 ratio (reduced CD8-positive cell numbers) in the nonpregnant endometrium of women who suffer unexplained infertility (Klentzeris et al, 1994) and recurrent miscarriage (Lachapelle et al, 1996;Quenby et al, 1999). In decidua associated with pregnancy loss, several studies have reported no difference in decidual CD3-positive numbers in women with recurrent (Quack et al, 2001) or sporadic (Vassiliadou and Bulmer, 1998b;Scaife et al, 2004) miscarriage compared to normal early pregnancy.…”

Section: T Lymphoctyes In Pathological Pregnancymentioning

confidence: 99%