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Published online before print September 12, 2003

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(Journal of Leukocyte Biology. 2003;74:998-1007.)
© 2003 by Society for Leukocyte Biology

Distinctive response of naïve lymphocytes from cord blood to primary activation via TCR

Department of Immunology, Institut de Recerca Hospital Sant Pau, Barcelona, Spain

¹Correspondence: Department of Immunology, Hospital Sant Pau, Pare Claret 167, Barcelona-08025, Spain. E-mail: svidal{at}hsp.santpau.es

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.

Key Words: human • T lymphocytes • cellular activation

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