title: Differing functional recovery of donor-derived immune cells after purified haploidentical and fully mismatched hematopoietic stem cell transplantation in mice.
abstract: Functional recovery of the immune system is critical for long-term survival in hematopoietic stem cell transplant recipients. In this study, two donor-recipient allogeneic transplant settings (haploidentical and fully mismatched) are used to investigate the functional activity of donor-derived 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).Ovalbumin-specific immunoglobulin G, polyclonal immunoglobulin isotypes, and B- and T-cell proliferation were examined on the recipients who received haploidentical or fully mismatched HSC.A severe deficiency of antigen-specific immunoglobulin response occurs in fully engrafted mice that received KTLS HSC from fully mismatched, but not haploidentical, donors. This lack of B-cell-specific immunity is not due to a deficiency of polyclonal immunoglobulins in serum. B cells from both fully mismatched and haploidentical recipients proliferate normally after 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 weaker than that of their untransplanted controls. However, T cells from haploidentical recipients respond normally to anti-CD3. This study demonstrates that numerical recovery of donor-derived cells in the periphery of recipients does not represent a functional reconstitution, particularly in animals that receive fully mismatched transplants. Defects of specific B-cell immunity and T-cell proliferation are observed in fully mismatched, purified HSC transplant recipients with a quantitative recovery within the normal range of donor-derived lymphocytes.
authors.affiliation: Program in T cell Therapeutics, SyStemix, Inc. (a Novartis company), Palo Alto, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Bowers
authors.forename: S
authors.initials: S
authors.lastname: Tamaki
authors.forename: A
authors.initials: A
authors.lastname: Coward
authors.forename: H
authors.initials: H
authors.lastname: Kaneshima
authors.forename: C C
authors.initials: CC
authors.lastname: Chao
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D007109:Immunity; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010047:Ovalbumin