Naive CD4+ cells from cord blood can generate competent Th effector cells.
BACKGROUND
Umbilical cord blood (UCB) cells have been increasingly used as a source of hematopoietic stem cells for allogeneic transplantation. Previous reports suggest that the low risk of graft-versus-host disease in patients that received cord blood cells seems related to the distinctive nature of cord blood T cells.


METHODS
To analyze the maturation of CD4+CD45RA+ cord blood cells, we performed an in vitro differentiation assay to compare the generation of Th effector cells strictly from UCB and adult peripheral blood (APB) CD4+CD45RA+ cells.


RESULTS
During the maturation into effector cells, UCB and APB cells acquired a comparable activation level determined by the expression pattern of CD69, CD40L, OX40 and CD62L as well as PD1 and CTLA-4 molecules. Moreover, the expression of CD45RO isoform was induced in most activated effector cells from both UCB and APB. OKT3-restimulated effector cells generated from naive UCB expressed higher levels of CD25 coinciding with the secretion of higher amounts of IL-2. Effector cells from both origins consisted of heterogeneous populations with similar frequencies of Th1 and Th2 cytokine producing cells, secreting equivalent levels of IL-4, IL-5 and IFNgamma. Although, higher levels of IL-10 were detected in the cytokine mRNA profile and in the supernatants of OKT3-restimulated UCB effector cells, blocking endogenous IL-10 with anti-IL-10 mAbs enhanced significantly the proliferative response of UCB as well as APB effector cells (P < 0.05).


CONCLUSIONS
These results indicated that Th effector cells generated from naive UCB cells were intrinsically as competent as naive APB to respond to TCR-mediated stimulation. In addition, UCB effector cells produced higher IL-10 but its inhibitory effect on proliferation may be partially compensated by the higher production of IL-2 and enhanced expression of CD25.
Cantó
Elisabet
E
Department of Immunology, Institut Recerca i Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Rodríguez-Sánchez
José L
JL
Vidal
Sílvia
S
D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell