Reconstitution of the immune system after murine allogeneic umbilical cord blood transplantation

Abstract

    The ability of murine allogeneic umbilical cord blood cells (UCBCs) to reconstitute the immune system was investigated. UCBCs obtained from fetuses of C57BL/6 (B6; H-2^b) mice, which were transgenic for green fluorescent protein (GFP), were transplanted into RAG2 (-/-) BALB/c mice (H-2^d). After transplantation, flow cytometric analysis revealed successful reconstitution of phenotypically mature GFP-positive immune cells of donor origin, including T cells, B cells, monocytes, and granulocytes in the peripheral blood of the recipient mice. Analysis of functional maturation of lymphocytes revealed that 2,4,6-trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH)-immunized UCBC-transplanted recipients produced both TNP-specific IgM and IgG antibodies. These results indicated that the recipient mice were capable of mounting antibody responses to T-dependent antigens; further, Ig class switching from IgM to IgG confirmed that both B cells and CD4⁺ helper T cells derived from allogeneic UCBCs were immunologically competent. Furthermore, mice transplanted with allogeneic UCBCs accepted skin grafts from both B6 and BALB/c mice. However, these chimeric mice completely rejected skin grafts from third party C3H/HeJ (H-2^k) mice, indicating the presence of functional CD8⁺ killer T cells as well as CD4⁺ helper T cells. In terms of potential clinical application, our results indicate that allogeneic UCBC transplantation can enable recovery of the normal immune system in recipients.