Analysis of Graft-versus-host Disease (GVHD) and Graft Rejection Using MHC Class I-deficient Mice

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 1998 Jul 2

PMID 9649180

Citations 1

Authors

S Shenoy

K Desch

B Duffy

P Thorson

T Mohanakumar

Affiliations

Soon will be listed here.

Abstract

GVHD is a major complication in allogeneic bone marrow transplantation (BMT). MHC class I mismatching increases GVHD, but in MHC-matched BMT minor histocompatibility antigens (mH) presented by MHC class I result in significant GVHD. To examine the modification of GVHD in the absence of cell surface MHC class I molecules, beta2-microglobulin-deficient mice (beta2m(-/-)) were used as allogeneic BMT recipients in MHC- and mH-mismatched transplants. Beta2m(-/-) mice accepted MHC class I-expressing BM grafts and developed significant GVHD. MHC (H-2)-mismatched recipients developed acute lethal GVHD. In contrast, animals transplanted across mH barriers developed indolent chronic disease that was eventually fatal. Engrafted splenic T cells in all beta2m(-/-) recipients were predominantly CD3+alphabetaTCR+CD4+ cells (15-20% of all splenocytes). In contrast, CD8+ cells engrafted in very small numbers (1-5%) irrespective of the degree of MHC mismatching. T cells proliferated against recipient strain antigens and recognized recipient strain targets in cytolytic assays. Cytolysis was blocked by anti-MHC class II but not anti-CD8 or anti-MHC class I monoclonal antibodies (MoAbs). Cytolytic CD4+ T cells induced and maintained GVHD in mH-mismatched beta2m(-/-) mice, supporting endogenous mH presentation solely by MHC class II. Conversely, haematopoietic beta2m(-/-) cells were unable to engraft in normal MHC-matched recipients, presumably due to natural killer (NK)-mediated rejection of class I-negative cells. Donor-derived lymphokine-activated killer cells (LAK) were unable to overcome graft rejection (GR) and support engraftment.

Citing Articles

T cell immunotherapeutic populations control viral infections in bone marrow transplant recipients.

Slobod K, Benaim E, Woodruff L, Nooner S, Houston J, Holladay M Immunol Res. 2002; 24(3):289-301.

PMID: 11817326 DOI: 10.1385/IR:24:3:289.

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