Functional and quantitative differences of regulatory T cells in fertile women and those with reproductive failure upon in vitro expansion

ARRUVITO LOURDES; PALADINO NATALIA; FLORES ANA CLAUDIA; FAINBOIM LEONARDO

Río de Janeiro, Brazil

Congreso; 13th International Congress of Immunology; 2007

We recently demonstrated that during the menstrual cycle, regulatory T cells (Treg) from fertile women are expanded in tight correlation with their serum levels of estradiol. In spite of normal serum levels of this hormone, women who have had recurrent spontaneous abortions (RSA)  not only failed to expand but also showed a decreased suppressor function of their Treg. In this study we investigated the capacity of Treg from fertile and RSA women to expand in response to IL-2, by using an in vitro expansion model previously reported by us. We observed that after 10 days of culture, the expression of CD4+CD25+ Foxp3+ Tregs expanded from a basal frequency of 4.7±0.7% (n=10) to 20.55±2.4% (ratio expanded/basal=4.37; p<0.0001). In contrast RSA women showed a very limited expansion from 3.43±0.6% to 6.72±2.5% (n=11; ratio expanded/basal 1.93, p=NS). As expected, this low expansion of Treg was accompanied by a deficient suppressor capacity compared with expanded Tregs from fertile women.  Interestingly, after RSA patients were treated with 9-12 doses of paternal PBMC (each dose containing ~1.2x108 PBMCs) it was observed an expansion ratio that was quite similar to fertile women (ratio expanded/basal= 4.7). In conclusion, we demonstrate that the previously reported deficiency in the expansion of Treg in RSA patients seems to be independent of estradiol and might be caused by an abnormal signalling through IL-2. Paternal immunotherapy appears to reverse this lack of response and represents a useful model to gain an insight into the in vivo Treg homeostasis.