Title
Partial versus full allogeneic hemopoietic chimerization is a preferential means to inhibit type 1 diabetes as the latter induces generalized immunosuppression
Academic Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Medicine, Diabetes Division; Department of Pathology
Publication Date
2006-11-04
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
10.4049/jimmunol.177.10.6675
Source
J Immunol. 2006 Nov 15;177(10):6675-84.
Journal/Book/Conference Title
Journal of immunology (Baltimore, Md. : 1950)
Related Resources
PubMed ID
17082580
Repository Citation
Serreze DV, Osborne MA, Chen Y, Chapman HD, Pearson T, Brehm MA, Greiner DL. (2006). Partial versus full allogeneic hemopoietic chimerization is a preferential means to inhibit type 1 diabetes as the latter induces generalized immunosuppression. GSBS Student Publications. https://doi.org/10.4049/jimmunol.177.10.6675. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1096