The traditional paradigm suggests that during normal pregnancy maternal immunological tolerance of the allogenic fetus is association with a maternal T-lymphocyte shift from a Th1 to a Th2 phenotype, with the opposite effect reported in patients with recurrent miscarriage. However, studies on maternal peripheral blood are conflicting. In the present study, we characterized the maternal CD4 T-cell effector subsets, including the recently described Th17 subset, during normal pregnancy (cross-sectional cohort, n=71; longitudinal cohort, n=17) and contrasted this with women with recurrent miscarriage (n=24). Longitudinal analysis of peripheral blood from normal pregnancy demonstrated a fall in the percentage of Th17 cells between the first and second trimester (P≤0.05), but no significant changes were observed across gestation or the post-natal period in Th1 or Th2 subsets. In contrast, in women with a history of recurrent miscarriage, an elevated proportion of Th17 (0.314% compared with 0.097%; P=0.0009) and Th1 (12.4% compared with 5.3%; P=0.0002) cells was detected. The suggestion that Th17 cells may have a role in the normal events of implantation and early pregnancy requires further evaluation and mechanistic studies. The results of the present study, by conducting a careful longitudinal analysis, demonstrate that a peripheral Th1/Th2 shift is not a requirement for normal pregnancy. By contrast, the profound increase in Th1 and Th17 cells in women with recurrent miscarriage indicates that peripheral immunological dysfunction may be important in this group specifically, and these assays may be important in guiding therapeutic interventions in this group and warrant further investigation to determine whether they are predictive of outcome or responses to immunomodulatory therapy.
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Research Article|
November 01 2013
Profile of maternal CD4 T-cell effector function during normal pregnancy and in women with a history of recurrent miscarriage
David Lissauer;
*Centre for Women's and Children's Health, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
Correspondence: Dr David Lissauer (email [email protected]).
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Oliver Goodyear;
Oliver Goodyear
†School of Cancer Sciences, University of Birmingham, Birmingham B15 2TG, U.K.
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Rahela Khanum;
Rahela Khanum
†School of Cancer Sciences, University of Birmingham, Birmingham B15 2TG, U.K.
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Paul A. H. Moss;
Paul A. H. Moss
†School of Cancer Sciences, University of Birmingham, Birmingham B15 2TG, U.K.
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Mark D. Kilby
Mark D. Kilby
*Centre for Women's and Children's Health, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
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Publisher: Portland Press Ltd
Received:
July 15 2013
Accepted:
August 20 2013
Accepted Manuscript online:
August 20 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 126 (5): 347–354.
Article history
Received:
July 15 2013
Accepted:
August 20 2013
Accepted Manuscript online:
August 20 2013
Citation
David Lissauer, Oliver Goodyear, Rahela Khanum, Paul A. H. Moss, Mark D. Kilby; Profile of maternal CD4 T-cell effector function during normal pregnancy and in women with a history of recurrent miscarriage. Clin Sci (Lond) 1 March 2014; 126 (5): 347–354. doi: https://doi.org/10.1042/CS20130247
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