Selective elimination of non-lpr lymphoid cells in mice undergoing lpr-mediated graft-vs-host disease

Journal Article · Tue Sep 01 04:00:00 EDT 1987 · J. Immunol.; (United States)

OSTI ID:6243534

Perkins, D L; Michaelson, J; Glaser, R M; Marshak-Rothstein, A

The transfer of lpr BM stem cells into lethally irradiated non-lpr recipients (including the congenic MRL/+ differing only at the lpr locus) causes GVHD characterized by a wasting syndrome. In this study we investigated the interaction between the autoimmune (lpr) and normal (A-Thy) B, T, and RBC cell lineages in two types of radiation chimeras: MRL/lpr plus A-Thy----(MRL/lpr X A-Thy)F1 and MRL/+ plus A-Thy----(MRL/lpr X A-Thy)F1. Analysis of B cell repopulation by competitive RIA of serum Igh-1 allotype showed that both the MRL and the A-Thy donor cells initially engrafted. However, by 2 to 4 mo post-transplantation the normal A-Thy allotype was barely detectable (reduced greater than 2 orders of magnitude), whereas the autoimmune MRL/lpr allotype persisted at normal levels. Similarly, investigation of the donor origin of peripheral blood T cells by two-color flow cytometry showed that by 8 mo post-transplantation normal A-Thy T cells had been eliminated and only MRL/lpr T cells were present in the circulation. In contrast, erythrocytes from both the MRL/lpr and A-Thy donor strains successfully engrafted the F1 recipients and persisted until the termination of the study. Control chimeras transplanted with a mixture of MRL/+ plus A-Thy BM were stably engrafted with both donor strains in both the erythroid and lymphoid populations. Additional experiments in which either B6/lpr or MRL/lpr (and B6/+ or MRL/+ control) BM cells were transferred into (MRL/lpr X B6/+)F1 and (MRL/lpr X B6/lpr)F1 recipients demonstrated that the development of GVHD was not simply due to increased alloreactivity by the lpr donor cells. In these chimeras only the recipients heterozygous (but not homozygous) for the lpr gene developed lpr-GVHD, although both types of recipients had identical genotypes except at the lpr locus.

• Research Organization: Boston Univ. School of Medicine, MA
• OSTI ID: 6243534
• Journal Information: J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 139:5; ISSN JOIMA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CELL FLOW SYSTEMS
CHIMERAS
CONNECTIVE TISSUE CELLS
ERYTHROCYTES
GENOTYPE
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
IMMUNOASSAY
IMMUNOLOGY
IRRADIATION
ISOTOPE APPLICATIONS
LETHAL IRRADIATION
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MOSAICISM
ORGANS
PHENOTYPE
RADIATION CHIMERAS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RODENTS
SOMATIC CELLS
STEM CELLS
TISSUES
TRACER TECHNIQUES
TRANSPLANTS
VERTEBRATES