Prevention of Spontaneous Abortion in the CBADBA/2 Mouse Model by Intravaginal TGF- beta and Local Recruitment of CD4+8+ FOXP3+ Cells

• Published in: American journal of reproductive immunology (1989) 2008-06, Vol.59 (6), p.525-534
• Main Authors: Clark, David A, Fernandez, Jason, Banwatt, Daljeet
• Format: Article
• Language: English
• Subjects: Salmonella enteritidis
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/j.1600-0897.2008.00582.x

ProblemActivation of latent transforming growth factor (TGF)- beta 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- beta , and a critical test of the hypothesis was required. The purpose of the present study was to directly test the effect of pure TGF- beta .Method of studyPharmaceutical grade bioactive TGF- beta 3 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- beta 3 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- beta 3 in 0.1% BSA-PBS or 20ng 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- beta s, had some activity, and could reduce availability of added TGF- beta 3. CD11c dendritic cells, CD3+ T cells, and CD25+ cells were recruited to the vaginal wall by 48hr after TGF- beta 3 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- beta 3, stimulated a physiological polymorphonuclear leukocyte exudate.ConclusionIntravaginal bioactive TGF- beta 3 can enhance success of pregnancy in vivo in an established model of abortion. The result could be explained by the independent ability of TGF- beta to promote a regulatory T-cell response.