Date Published: February 18, 2018
Publisher: John Wiley and Sons Inc.
Author(s): Marta Rodriguez‐Garcia, Jared M. Fortier, Fiona D. Barr, Charles R. Wira.
As 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.
Epidemiological studies show a global increase in the incidence of sexually transmitted infections (STIs), including new HIV infections, in older adults (CDC, 2016; Ghosh, Rodriguez‐Garcia & Wira, 2013). As people age, the systemic immune system undergoes progressive dysregulation that results in increased susceptibility to infections and malignancies and reduced responses to vaccination and increased general inflammation (Ghosh et al., 2013). However, the extent to which aging affects mucosal cell‐mediated immune protection in the female reproductive tract (FRT) is unknown and represents a critical gap in our knowledge for the development of preventive and/or treatment strategies against STIs for women of all ages.
Our study demonstrates the novel compartmentalization and regulation of CD103+ T cells and DCs in the FRT before and after menopause. Because women have a uniquely long postreproductive survival potential (Walker & Herndon, 2008), human studies are critical to unravel immunological changes induced by menopause and aging. Recognizing that human and mouse studies indicate that anatomical location influences T‐cell immunity, the studies presented here focus on tissues from three distinct anatomical sites in the FRT, from women between 27 and 77 years old, to define the extent to which CD103+ T cells and DCs are uniquely regulated in the FRT over time.
The authors declared no conflict of interest.
MR‐G designed the research; MR‐G, JMF, and FB conducted experiments and acquired data; MR‐G, JMF, and CRW analyzed data; MR‐G and CRW wrote the manuscript.