Faculty Collaboration Database

Partial versus full allogeneic hemopoietic chimerization is a preferential means to inhibit type 1 diabetes as the latter induces generalized immunosuppression. J Immunol 2006 Nov 15;177(10):6675-84

Date

11/04/2006

Pubmed ID

17082580

DOI

10.4049/jimmunol.177.10.6675

Scopus ID

2-s2.0-33750818891 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

In both humans and NOD mice, particular combinations of MHC genes provide the primary risk factor for development of the autoreactive T cell responses causing type 1 diabetes (T1D). Conversely, other MHC variants can confer dominant T1D resistance, and previous studies in NOD mice have shown their expression on hemopoietically derived APC is sufficient to induce disease protection. Although allogeneic hemopoietic chimerization can clearly provide a means for blocking T1D development, its clinical use for this purpose has been obviated by a requirement to precondition the host with what would be a lethal irradiation dose if bone marrow engraftment is not successful. There have been reports in which T1D-protective allogeneic hemopoietic chimerization was established in NOD mice that were preconditioned by protocols not including a lethal dose of irradiation. In most of these studies, virtually all the hemopoietic cells in the NOD recipients eventually converted to donor type. We now report that a concern about such full allogeneic chimeras is that they are severely immunocompromised potentially because their T cells are positively selected in the thymus by MHC molecules differing from those expressed by the APC available in the periphery to activate T cell effector functions. However, this undesirable side effect of generalized immunosuppression is obviated by a new protocol that establishes without a lethal preconditioning component, a stable state of mixed allogeneic hemopoietic chimerism sufficient to inhibit T1D development and also induce donor-specific tolerance in NOD recipients.

Author List

Serreze DV, Osborne MA, Chen YG, Chapman HD, Pearson T, Brehm MA, Greiner DL

Author

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line
Cricetinae
Dendritic Cells
Diabetes Mellitus, Type 1
Female
Hematopoietic Stem Cell Transplantation
Hemocyanins
Lymphocyte Depletion
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Radiation Chimera
Skin Transplantation
Thymus Gland
Transplantation Tolerance