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

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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.
Funding Information
  • FIS (00/0583)
  • Fondo Investigaciones Sanitarias