GSBS Student Publications

Title

Partial versus full allogeneic hemopoietic chimerization is a preferential means to inhibit type 1 diabetes as the latter induces generalized immunosuppression

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Medicine, Diabetes Division; Department of Pathology

Date

11-4-2006

Document Type

Article

Medical Subject Headings

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

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.

Rights and Permissions

Citation: J Immunol. 2006 Nov 15;177(10):6675-84.

Related Resources

Link to Article in PubMed

Journal Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

17082580