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.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Bowers E,Tamaki S,Coward A,Kaneshima H,Chao CC

doi

10.1016/s0301-472x(00)00554-3

keywords:

subject

Has Abstract

pub_date

2000-12-01 00:00:00

pages

1481-9

issue

12

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(00)00554-3

journal_volume

28

pub_type

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