title: Paternal antigen-specific proliferating regulatory T cells are increased in uterine-draining lymph nodes just before implantation and in pregnant uterus just after implantation by seminal plasma-priming in allogeneic mouse pregnancy.
abstract: Paternal antigen-specific regulatory T (PA-specific Treg) cells play an important role in feto-maternal tolerance. To detect the PA-specific Tregs, female BALB/c mice were mated with male DBA/2 mice. Mls Ia antigen on DBA/2 mice is recognized by the T-cell receptor Vβ6; thus, CD4(+)Foxp3(+)Vβ6(+) cells are recognized as PA-specific Treg cells. CD4(+)CD25(+)Vβ6(+) cells effectively suppressed the allo-reactive proliferation of lymphocytes compared with that of CD4(+)CD25(+)Vβ6(-) cells. Vβ6(+) PA-specific Treg cells expressed CCR4 and CCR5 on their surface. The frequency of Ki67(+) PA-specific Treg cells among Treg cells was significantly increased in draining lymph nodes on day 3.5 post-coitus (pc; 6.8±1.1%, p<0.05) and day 5.5 pc (7.2±1.1%, p<0.05) in allogeneic pregnant mice compared with that in nonpregnant mice (2.7±0.2%). The frequency of Ki67(+) PA-specific Treg cells in the uterus increased significantly after day 5.5 pc in allogeneic pregnant mice compared with that in nonpregnant mice (8.8±2.8% vs. 1.2±1.3%, p<0.05). However, Ki67(-)PA-specific Tregs did not change during pregnancy. To analyze the role of seminal fluid or sperm in Treg expansion, female BALB/c mice were mated with vasectomized DBA/2 male mice (VAS) or seminal vesicle-excised DBA/2 male mice (SVX). The frequency of Ki67(+) PA-specific Treg cells did not increase in draining lymph nodes or uterus in BALB/c×DBA/2 (SVX) allogeneic mating mice. These findings suggest that the priming by seminal fluid is important for the induction of proliferating PA-specific Tregs in uterine-draining lymph nodes just before implantation and pregnant uterus after implantation, resulting in successful implantation and the maintenance of allogeneic pregnancy.
authors: Department of Obstetrics and Gynecology, University of Toyama, Toyama 930-0194, Japan.
authors: Tomoko
authors: T
authors: Shima
authors: Department of Obstetrics and Gynecology, University of Toyama, Toyama 930-0194, Japan.
authors: Kumiko
authors: K
authors: Inada
authors: Department of Obstetrics and Gynecology, University of Toyama, Toyama 930-0194, Japan.
authors: Akitoshi
authors: A
authors: Nakashima
authors: Department of Obstetrics and Gynecology, University of Toyama, Toyama 930-0194, Japan.
authors: Akemi
authors: A
authors: Ushijima
authors: Department of Obstetrics and Gynecology, University of Toyama, Toyama 930-0194, Japan.
authors: Mika
authors: M
authors: Ito
authors: Department of Obstetrics and Gynecology, University of Toyama, Toyama 930-0194, Japan.
authors: Osamu
authors: O
authors: Yoshino
authors: Department of Obstetrics and Gynecology, University of Toyama, Toyama 930-0194, Japan. Electronic address: s30saito@med.u-toyama.ac.jp.
authors: Shigeru
authors: S
authors: Saito
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D010290:Parents; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D054398:Receptors, CCR4 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D012661:Semen / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014599:Uterus / Q000276:immunology*; D014659:Vasectomy
chemical_list: C000592874:CCR5 protein, mouse; C515355:Ccr4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007519:Isoantigens; D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054398:Receptors, CCR4; D019713:Receptors, CCR5
keywords: Chemokine receptor; Feto-maternal tolerance; Paternal antigen; Regulatory T cells; Seminal fluid