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Publication : Resistance to lipopolysaccharide-induced preterm delivery mediated by regulatory T cell function in mice.

First Author  Bizargity P Year  2009
Journal  Biol Reprod Volume  80
Issue  5 Pages  874-81
PubMed ID  19144956 Mgi Jnum  J:149636
Mgi Id  MGI:3848777 Doi  10.1095/biolreprod.108.074294
Citation  Bizargity P, et al. (2009) Resistance to lipopolysaccharide-induced preterm delivery mediated by regulatory T cell function in mice. Biol Reprod 80(5):874-81
abstractText  Intrauterine or intraperitoneal administration of lipopolysaccharide (LPS) into normal mice at midgestation induces preterm delivery (PTD) within 24 h through a mechanism dependent on Toll-like receptor signaling and expression of inflammatory cytokines. The exact participants in the cellular network involved in PTD are not known. Although the activities of innate immune cells are thought to be important, the extent to which this process depends on T and B cells has yet to be examined. Mice deficient in T and B cells due to genetic deficiency in the recombination activating gene 1 (Rag1(-/-)) were given LPS intraperitoneally on Day 15 of gestation and found to be susceptible to LPS-induced PTD. This was found to involve many of the inflammatory mediators reported as important in normal mice. Moreover, at a low dose (3 microg), pregnant Rag1(-/-) mice were found to be more susceptible to PTD than a cohort of normal mice on the same genetic background. This increased susceptibility was partially reversed by transfer, on Day 10 of gestation, of whole lymphocytes or purified CD4(+) T cells. Transfer of purified CD4(+) T cells to Rag1(-/-) mice resulted in a uterine draining node population of FOXP3(+) cells, suggesting that these cells may contribute to resistance to LPS-induced PTD. Overall, the data suggest that, although T and B lymphocytes are not critical positive regulators of LPS-induced PTD, CD4(+) T cells play a protective and regulatory role, and thus could be a target for preventive or therapeutic manipulation.
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