Immunology

Blockade of CD86 Signaling Facilitates a Th2 Bias at the Materno-Fetal Interface and Expands Peripheral CD4⁺CD25⁺ Regulatory T Cells to Rescue Abortion-Prone Fetuses

Abstract
Intervention in B7 (CD80/CD86)/B7-ligand (CD28/CTLA-4) pathways is an effective way of preventing unwanted immune responses, such as allograft rejection. Pregnancy maintenance represents a situation of maternal tolerance to the fetal allograft, which is accompanied by a Th2 bias at the materno-fetal interface. Here, the costimulatory signal of CD86 was selectively blocked, and that of CD80 was kept unimpaired by administration of anti-murine CD86 monoclonal antibody at the early gestational stage in abortion-prone CBA/JxDBA/2 matings and normal pregnant CBA/JxBALB/c matings. It was demonstrated that the blockade in vivo of CD86 costimulation could suppress maternal immune attack to the fetus by shifting cytokines from Th1 predominance to Th2 bias at the materno-fetal interface, and expanding peripheral CD4⁺CD25⁺ regulatory T cells, which play an important role in the development and maintenance of the materno-fetal tolerance. Furthermore, the expression of CD28 and its ligands CD80/CD86 on peripheral lymphocytes was down-regulated, whereas that of CTLA-4 was up-regulated, which might facilitate the suppressive effect of CD4⁺CD25⁺ regulatory T cells on the allo-reactive T cells. The materno-fetal immuno-tolerance induced by CD86 blockade decreased fetal resorption in CBA/JxDBA/2 matings, but did not affect normal pregnant CBA/JxBALB/c matings. These results suggest that selective blockade of CD86 costimulation leads to the maternal immune tolerance to embryo antigen, and might contribute to a rational immuno-regulatory regimen for recurrent spontaneous abortion.

Key words: Embryo • Immunology • Pregnancy • Cytokines

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