132. IMMUNE-DEVIATING CYTOKINES DETERMINE THE MATERNAL T CELL RESPONSE DURING PREGNANCY AND TOLERANCE OR REJECTION OF THE CONCEPTUS
L. M. Moldenhauer A , J. D. Hayball B C and S. A. Robertson AA Research Centre for Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, SA, Australia
B Experimental Therapeutics Laboratory, Hanson Institute, Adelaide, SA, Australia
C Sansom Institute, University of South Australia, Adelaide, SA, Australia
Reproduction, Fertility and Development 21(9) 51-51 https://doi.org/10.1071/SRB09Abs132
Published: 26 August 2009
Abstract
In healthy pregnancies the maternal immune system establishes paternal antigen-specific tolerance allowing survival of the semi-allogeneic conceptus. The cytokine environment is a key factor in determining the phenotype of antigen-specific lymphocytes, influencing the development of either cytotoxic or tolerogenic cells. We hypothesized that the cytokine environment at the time of priming to paternal antigens influences the phenotype of the maternal T cell response and pregnancy outcome. Transgenic Act-mOVA male mice expressing chicken ovalbumin (OVA) ubiquitously provided OVA as a model paternal antigen. OVA is present within the semen of Act-mOVA mice and is inherited and expressed by the conceptus tissue. OVA-reactive CD8+ OT-I T cells were activated with OVA in the presence of various immune-deviating cytokines in vitro, before transfer at 3.5 dpc to C57Bl/6 (B6) females gestating OVA-expressing fetuses. Pregnant mice received either naïve OT-I T cells, cytotoxic OT-I T cells stimulated in vitro in the presence of IL-2 or OT-I T cells stimulated in vitro in the presence of TGFβ1 and IL-10, two factors present in the uterus and associated with immune tolerance. Immunohistochemistry was utilized to demonstrate that OT-I T cells infiltrate into the implantation site. Cytotoxic OT-I T cells caused fetal loss, while OT-I T cells activated in vivo or in vitro with TGFβ1 and IL-10 did not cause fetal loss. Additionally, cytotoxic OT-I T cells did not affect B6 x B6 matings, demonstrating the antigen-specific nature of the T cell-mediated fetal loss. Collectively these experiments show that maternal antigen-reactive T cells activated in vivo in the cytokine environment of the mated uterus are tolerogenic, not cytotoxic, and implicate TGFβ1 and IL-10 as key elements of that environment. We conclude that the cytokine environment at the time of priming to paternal antigens influences the T cell phenotype and impacts upon maternal immune tolerance and fetal survival.
