ORIGINAL ARTICLE: Prevention of Spontaneous Abortion in the CBA × DBA/2 Mouse Model by Intravaginal TGF‐β and Local Recruitment of CD4+ 8+ FOXP3+ Cells
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ProblemActivation of latent transforming growth factor (TGF)‐β in seminal plasma has been suggested by Robertson et al. to promote maternal tolerance to paternal antigens. A possible consequence reported by Tremellen et al. is increased pregnancy rates in women undergoing IVF. A decreased spontaneous abortion rate has also been postulated. Seminal plasma contains many factors besides TGF‐β, and a critical test of the hypothesis was required. The purpose of the present study was to directly test the effect of pure TGF‐β.Method of studyPharmaceutical grade bioactive TGF‐β3 with a bovine serum albumin (BSA) carrier 0.1–1% in phosphate‐buffered saline (PBS) was given into the vaginal tract of CBA/J female mice at the time of mating with DBA/2 males. One microgram Salmonella enteritidis lipopolysaccharide was given intraperitoneally to augment occult losses and spontaneous resorptions assessed on day 13.5 of pregnancy. The effect of TGF‐β3 on recruitment of lymphomyeloid cells to the vaginal wall and vaginal lumen of unmated mice in estrus was assessed using immunohistochemistry and flow cytometry.ResultsTwo nanogram of intravaginal TGF‐β3 in 0.1% BSA–PBS or 20 ng in 1% BSA–PBS reduced abortion rates. Protection was comparable to that achieved by immunization with BALB/c spleen cells. Fraction V BSA, a binder of TGF‐βs, had some activity, and could reduce availability of added TGF‐β3. CD11c dendritic cells, CD3+ T cells, and CD25+ cells were recruited to the vaginal wall by 48 hr after TGF‐β3 treatment, and cellularity of vaginal exudates increased. Foxp3+ cells were present in increased numbers, and appeared to be CD8+ and CD4+ 8+. Semen, but not TGF‐β3, stimulated a physiological polymorphonuclear leukocyte exudate.ConclusionIntravaginal bioactive TGF‐β3 can enhance success of pregnancy in vivo in an established model of abortion. The result could be explained by the independent ability of TGF‐β to promote a regulatory T‐cell response.
