title: CD40, CD80, and CD86 costimulatory molecules are differentially expressed on murine splenic antigen-presenting cells during the pre-implantation period of pregnancy, and they modulate regulatory T-cell abundance, peripheral cytokine response, and pregnancy outcome.
abstract: OBJECTIVE
  The object of the study was to investigate the costimulatory phenotype of spleen antigen-presenting cells (APCs) in mice after mating and the influence of costimulatory signal blocking on pregnancy outcome, cytokine production, and Treg cell concentration.
  
  
  METHODS
  The levels of CD40, CD80, and CD86 on spleen APCs at day 0.5 and 3.5 after mating (C57BL/6Jx DBA/2J and C57BL/6JxBalb/c) were assessed by flow cytometry and RT-PCR. Blocking antibodies against costimulatory molecules were given i.p. at day 3.5 after mating. Pregnancy outcomes, blood cytokine (ELISA), and spleen Treg (flow cytometry) concentrations were examined at day 10.5 after mating.
  
  
  RESULTS
  Differential expression of costimulatory molecules on spleen APCs of mated v. pseudopregnant mice was observed mainly at day 3.5 after conception. Administration of anti-CD86 antibody lowered pregnancy outcome. Cytokine expression was modulated after administration of anti-CD86, anti-CD80 and anti-CD40 antibodies, whereas only anti-CD40 antibody changed the concentration of Treg lymphocytes and the level of Foxp3 protein expression.
  
  
  CONCLUSIONS
  Costimulatory phenotype of female spleen APCs is distinctly modulated after mating. Alteration of costimulatory signal derived from APCs during pre-implantation period of pregnancy may have an adverse effect on pregnancy outcome and the tolerogenic immune response.
authors: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors: Anna
authors: A
authors: Slawek
authors: Tomasz
authors: T
authors: Maj
authors: Anna
authors: A
authors: Chelmonska-Soyta
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis* / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011247:Pregnancy; D011256:Pregnancy Outcome; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines
keywords: antigen-presenting cells; costimulatory molecules; pregnancy; spleen