Transmaternal cell flow leads to antigen-experienced cord blood

Umbilical cord blood (UCB) is used for HSCT. It is known that UCB can comprise Ag-specific T cells. Here we question whether solely transmaternal cell flow may immunize UCB. Twenty-three female UCB samples were collected from healthy mothers and analyzed for minor histocompatibility Ag HY-specific responses. Forty-two of 104 tetramer(pos) T-cell clones, isolated from 16 of 17 UCB samples, showed male-specific lysis in vitro. Male microchimerism was present in 6 of 12 UCB samples analyzed. In conclusion, female UCB comprises HY-specific cytotoxic T cells. The immunization is presumably caused by transmaternal cell flow of male microchimerism present in the mother. The presence of immune cells in UCB that are not directed against maternal foreign Ags is remarkable and may explain the reported clinical observation of improved HSCT outcome with younger sibling donors.     

Depletion of recipient CD4+ but not CD8+ T lymphocytes prevents the development of cardiac allograft vasculopathy

BACKGROUND: We have described that chimeric rat hearts bearing recipient-type antigen-presenting cells (APCs) do not reject acutely, but develop cardiac allograft vasculopathy (CAV) in untreated recipients. This suggests that CAV is triggered either by CD8+ direct allorecognition or by CD4+ indirect allorecognition. To determine the allorecognition pathway responsible for CAV in this model, recipients of chimeric hearts underwent either CD8+ or CD4+ T cell depletion. METHODS: Chimeric hearts were created via bone marrow transplantation in two fully major histocompatibility-mismatched rat strain combinations. DA recipients were thymectomized and treated with Ox8 and Ox38 murine monoclonal antibodies, which deplete CD8+ and CD4+ T cells, respectively. Chimeric PVG hearts bearing DA APCs, abbreviated PVG(DA), were heterotopically transplanted into recipients undergoing thymectomy alone or recipients undergoing thymectomy plus either CD4+ or CD8+ T cell depletion. RESULTS: PVG(DA) allografts survived 100 days, but developed CAV in thymectomized recipients and in those permanently depleted of CD8+ T cells. In contrast, chimeric hearts transplanted into permanently CD4+ T cell-depleted recipients survived 100 days and demonstrated no evidence of CAV. CONCLUSIONS: In this specific strain combination, recipient CD8+ T cells are neither necessary nor sufficient for the development of CAV, whereas recipient CD4+ T cells are required for the development of CAV. These findings suggest that CAV is dependent on CD4+ indirect allorecognition and that CD8+ direct allorecognition stimulated by nonprofessional APCs plays a minor role.     

Comparison of decidual leukocytes following spontaneous vaginal delivery and elective cesarean section in uncomplicated human term pregnancy

The aim of this study was to quantify and compare leukocyte populations in term decidua basalis and parietalis obtained after spontaneous vaginal delivery (SVD) or elective cesarean section (CS) without labor. Decidua basalis and parietalis samples were obtained from placentas after SVD (n = 20) and after CS (n = 30). Following mechanical disaggregation, leukocytes were purified and stained with monoclonal antibodies. Percentages of leukocyte subclasses within the CD45(+) cell fraction and activated T cells were determined by flow cytometry. No differences were found in the percentages of CD45(+) cells or CD56(bright)CD16(-) uterine natural killer (NK) cells between decidua basalis from SVD and CS or between decidua parietalis from SVD and CS. In decidua basalis and parietalis from SVD, a significantly higher number of CD56(dim)CD16(+) NK cells was found compared to CS. In decidua basalis from SVD, there was a significantly lower percentage of CD14(+) cells and higher percentage of CD19(+) cells compared to CS. The percentage of CD3(+) T cells expressing CD25 or human leukocyte antigen (HLA)-DR was significantly decreased in decidua basalis and parietalis from SVD compared to CS. Comparison of decidua collected after SVD or CS suggests that labor is associated with dynamic changes in the distribution of decidual leukocytes, specifically NK and T cell subpopulations. In particular, the disappearance of the CD4(+)CD25(+) T cell population, which possibly contains a subpopulation of regulatory T cells, may contribute to the initiation of labor. Further investigation into factors affecting decidual leukocytes may expand our understanding of the immunological events at the maternal-fetal interface.