title: Distinctive response of naïve lymphocytes from cord blood to primary activation via TCR.
abstract: Umbilical cord blood (UCB) is now being considered an alternative to bone marrow for restoring hematopoiesis after myeloablative therapy. The lower risk of acute and chronic graft-versus-host disease in patients who received UCB cells seems related to the nature of UCB-T cells. Phenotypically, UCB-CD3+ cells are mostly naive (CD45RA+) and represent a transitional population between thymocytes and adult T cells. We examined the immune reactivity of highly purified, negatively selected CD4+CD45RA+ cells by mimicking activation via T cell receptor (TCR). All experiments included the extensively characterized adult peripheral blood (APB) cells as reference. On the contrary to APB, naive UCB-CD4+ cells were able to proliferate with anti-CD3 stimulation alone. With addition of interleukin (IL)-2 or costimulatory signal, both populations reached similar proliferation. Forty-eight hours after anti-CD3 stimulation, CD4+CD45RA+ from UCB, but not APB, showed characteristic blastic morphology and significant expression of CD25 on the surface. A low concentration of IL-2 was detected at 24 h by anti-CD3-stimulated UCB CD4+CD45RA+, which rapidly disappeared. By 72 h after activation, CD4+CD45RA+ UCB cells showed extensive apoptosis, whereas CD4+CD45RA+ APB cells showed low levels of apoptosis. Using RNase protection assay, we observed that CD95L levels were significantly higher in naive CD4+ cells from UCB than from APB after activation. However, neutralizing Fas-Fc protein was unable to inhibit anti-CD3-induced apoptosis, suggesting that this was a CD95-independent mechanism. These results indicate that UCB-CD4+CD45RA+ cells are able to start proliferating as a result of early IL-2 production after TCR engagement alone, but probably, as a result of the consumption of this IL-2, they undergo cell death.
authors.affiliation: Department of Immunology, Institut de Recerca Hospital Sant Pau, Pare Claret 167, Barcelona-08025, Spain. svidal@hsp.santpau.es
authors.forename: Elisabet
authors.initials: E
authors.lastname: Cantó
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Rodriguez-Sanchez
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidal
mesh_terms: D000328:Adult; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D012259:Ribonuclease, Pancreatic; D017493:Leukocyte Common Antigens; D013936:Thymidine