Differing functional recovery of donor-derived immune cells after purifiedhaploidentical and fully mismatched hematopoietic stem cell transplantation in mice

Objective. Functional recovery of the immune system is critical for long-te rm survival in hematopoietic stem cell transplant recipients. In this study , two donor-recipient allogeneic transplant settings (haploidentical and fu lly mismatched) are used to investigate the functional activity of donor-de rived B and T cells in animals grafted with purified c-kit(+), Thy 1.1(lo), Lin(-/lo), and Sca-1(+) hematopoietic stem cells (KTLS HSC). Materials and Methods. Ovalbumin-specific immunoglobulin G, polyclonal immu noglobulin isotypes, and B- and T-cell proliferation were examined on the r ecipients who received haploidentical or fully mismatched HSC. Results. A severe deficiency of antigen-specific immunoglobulin response oc curs in fully engrafted mice that received KTLS HSC from fully mismatched, but not haploidentical, donors, This lack of B-cell-specific immunity is no t due to a deficiency of polyclonal immunoglobulins in serum, B cells from both fully mismatched and haploidentical recipients proliferate normally af ter stimulation with anti-mu and the percentage of mature B cells is normal . The T-cell response to anti-CD3 in fully mismatched recipients was much w eaker than that of their untransplanted controls. However, T cells from hap loidentical recipients respond normally to anti-CD3. Conclusions. This study demonstrates that numerical recovery of donor-deriv ed cells in the periphery of recipients does not represent a functional rec onstitution, particularly in animals that receive fully mismatched transpla nts. Defects of specific B-cell immunity and T-cell proliferation are obser ved in fully mismatched, purified HSC transplant recipients with a quantita tive recovery within the normal range of donor-derived lymphocytes. (C) 200 0 International Society for Experimental Hematology. Published by Elsevier Science Inc.