An investigation of the relationship between recurrent spontaneous abortion and memory T follicular helper cells.

Abstract

Immune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells' function comes from immune-related diseases. However, the true physiological characteristics of memory Tfh cells and their mode of action in pregnancy remain unclear. Deciduas and blood were obtained from 25 recurrent spontaneous abortion (RSA) patients undergoing surgical abortion and 19 normal women in early pregnancy undergoing elective termination. RSA patients were grouped into antibody-positive patients and antibody-negative patients, respectively. The memory Tfh cells with the CD4+ CXCR5+ PD1+ CCR7- and CD4+ CXCR5+ PD-1+ ICOS+ phenotypes were assessed by flow cytometry. The B cells were evaluated by flow cytometry. A correlation analysis of the subsets of memory Tfh cells and B cells in antibody-positive RSA patients was made by the Pearson test. Memory Tfh cells with the CD4+ CXCR5+ PD1+ CCR7- and CD4+ CXCR5+ PD-1+ ICOS+ phenotypes showed a significant increase in RSA patients compared to women with a normal pregnancy who had chosen termination. When RSA patients were grouped according positive or negative antibodies, it was surprising to find that decidual CD4+ CXCR5+ PD-1+ ICOS+ memory Tfh cells significantly increased in RSA patients with positive antibody compared to RSA patients with negative antibody. However, the percentages of CD4+ CXCR5+ PD1+ CCR7- memory Tfh cells did not change in the deciduas of the two groups. Circulating and decidual B cells significantly increased in antibody-positive RSA patients compared with antibody-negative RSA patients. Correlation analysis indicated a strong association between the decidual CD4+ CXCR5+ PD-1+ ICOS+ memory Tfh cells and B cells in antibody-positive RSA patients. These new findings provide unique insights into memory Tfh cells in mediating feto-maternal immune tolerance.