J Exp Med. Dec 1, 1996; 184(6): 2393–2398.
Brief Definitive Reports
The Thymus Contains a High Frequency of Cells that Prevent Autoimmune Diabetes on Transfer into Prediabetic Recipients
From the *Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE United Kingdom; ‡Institute National de la Santé et de la Recherche Médicale U28, Hôpital Purpan, 31059, Toulouse, France; and §Infectious Disease Division, University of California, San Francisco, California 94143-0654
Received July 8, 1996; Revised September 23, 1996
Rats of the PVG.RT1u strain develop autoimmune diabetes when thymectomized at 6 wk of age and are rendered relatively lymphopenic by a cumulative dose of 1,000 rads 137Cs γ-irradiation given in four split doses. Previous studies have shown that the disease is prevented by the intravenous injection of 5 × 106 CD4+ CD45RC− TCRαβ+ RT6+ peripheral T cells from normal syngeneic donors. These cells have a memory phenotype and are presumably primed to some extrathymic antigen. However, we now report that the CD4+ CD8− population of mature thymocytes is a very potent source of cells, with the capacity to prevent diabetes in our lymphopenic animals. As few as 6 × 105 of these cells protect ~50% of recipients and the level of protection increases with cell dose. It appears that one characteristic of the intrathymic selection of the T cell repertoire is the generation of cells that regulate the autoimmune potential of peripheral T cells that have been neither clonally deleted intrathymically nor rendered irreversibly anergic in the periphery.
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Figure 1 CD4+CD8− thymocytes are more potent than peripheral CD4+CD45RC− T cells in protecting from diabetes. T cells subsets were negatively selected from TDLs or thymus from normal PVG.RT1u rats by rosette depletion as described (more ...)
Figure 2 Naive CD4+CD8− thymocytes are less potent in providing in vivo B cell help than primed peripheral CD4+ T cells. Primed CD4+ T cells and primed B cells were negatively selected from TDLs from PVG.RT1c rats primed with (more ...)
Comparison of Experimental and Theoretical Results on Control of Diabetes by CD4+CD8− Thymocytes