Transplantation tolerance can be induced in mice by grafting under the cover of nondepleting CD4 plus CD8 or CD154 mAbs. This tolerance is donor Ag specific and depends on a population of CD4+ regulatory T cells that, as yet, remain poorly defined in terms of their specificity, origin, and phenotype. Blocking of the Ag-specific response in vitro with an anti-CD4 mAb allowed T cells from monospecific female TCR-transgenic mice against the male Ag Dby, presented by H-2Ek, to express high levels of foxP3 mRNA. foxP3 induction was dependent on TGF-β. The nondepleting anti-CD4 mAb was also able to induce tolerance in vivo in such monospecific TCR-transgenic mice, and this too was dependent on TGF-β. As in conventional mice, acquired tolerance was dominant, such that naive monospecific T cells were not able to override tolerance. Splenic T cells from tolerant mice proliferated normally in response to Ag, and secreted IFN-γ and some IL-4, similar to control mice undergoing primary or secondary graft rejection. High levels of foxP3 mRNA, and glucocorticoid-induced TNFR superfamily member 18 (GITR)+ CD25+ T cells were found within the tolerated skin grafts of long-term tolerant recipients. These data suggest that regulatory T cells maintaining transplantation tolerance after CD4 Ab blockade can be induced de novo through a TGF-β-dependent mechanism, and come to accumulate in tolerated grafts.

CD4+CD25+ T cells have been proposed as the principal regulators of both self-tolerance and transplantation tolerance. Although CD4+CD25+ T cells do have a suppressive role in transplantation tolerance, so do CD4+CD25− T cells, although 10-fold less potent. Abs to CTLA-4, CD25, IL-10, and IL-4 were unable to abrogate suppression mediated by tolerant spleen cells so excluding any of these molecules as critical agents of suppression. CD4+CD25+ T cells from naive mice can also prevent rejection despite the lack of any previous experience of donor alloantigens. However, this requires many more naive than tolerized cells to provide the same degree of suppression. This suggests that a capacity to regulate transplant rejection pre-exists in naive mice, and may be amplified in “tolerized” mice. Serial analysis of gene expression confirmed that cells sorted into CD4+CD25+ and CD4+CD25− populations were distinct in that they responded to TCR ligation with very different programs of gene expression. Further characterization of the differentially expressed genes may lead to the development of diagnostic tests to monitor the tolerant state.

Introduction Sexuality is an important part of health and well-being. Sexual behavior modifies as pregnancy progresses, influenced by biological, psychological, and social factors. Aim To evaluate changes in sexual perceptions and activities during pregnancy and to determine sexual dysfunctions in that period. Main Outcome Measures Sexual perceptions (desire from the partner, feelings of attractiveness, and fear of sexual intercourse), sexual activities during pregnancy (sexual intercourse frequency, the most frequent sexual intercourse trimester, sexual activity during the birth week, type(s) of sexual intercourse, changes in sexual satisfaction and desire compared with the pre-pregnancy period, and changes in sexual intercourse frequency during each trimester compared with the pre-pregnancy period), and sexual dysfunctions. Methods Puerperal women were asked to anonymously complete a self-administered and structured questionnaire at the day of discharge from hospital. Results One hundred and eighty-eight women, aged between 17 years and 40 years with a mean age of 28.9 years, were analyzed. The first trimester was considered the most frequent period of sexual intercourse (44.7%), followed by the second trimester (35.6%). Fifty-five percent reported a decrease of sexual activity during the third trimester. Fear of sexual intercourse was referred by 23.4% of the women questioned. Sexual satisfaction was unchanged in 48.4% of the subjects and decreased in 27.7% (P <0.0001); sexual desire is reported to be unchanged in 38.8% and decreased in 32.5% (P = 0.196) of the population. Vaginal, oral, anal sex, and masturbation were performed by 98.3%, 38.1%, 6.6%, and 20.4% of the women, respectively. Conclusions We determined in our study that sexual satisfaction do not change in pregnancy compared with the pre-pregnancy patterns despite a decline of sexual activity during the third trimester. A discussion of expected changes in sexuality should be routinely done by the doctor in order to improve couples’ perception of possible sexual modifications induced by pregnancy.

The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.