ONTOGENY AND IMMUNOHISTOCHEMICAL LOCALIZATION OF THYMUS-DEPENDENT ANDTHYMUS-INDEPENDENT RT6+ CELLS IN THE RAT

RT6 is a cell surface alloantigen that identifies a regulatory subset of peripheral T cells in the rat. Diabetes-prone BB rats are deficient in peripheral RT6(+) T cells and develop spontaneous autoimmune insul in-dependent diabetes mellitus. Diabetes-resistant BB rats have normal numbers of RT6(+) T cells, and insulin-dependent diabetes mellitus ca n be induced in these animals by in vivo depletion of peripheral RT6() cells. Athymic rats are also severely deficient in peripheral RT6(+) T cells. Although very different with respect to the peripheral RT6() cell compartment, normal, athymic, and diabetes-prone BB rats all ge nerate RT6(+) intestinal epithelial lymphocytes (IELs). The goal of th ese studies was to analyze the ontogeny of RT6(+) IELs and peripheral lymphoid cells by in situ immunohistochemistry. We observed the follow ing. 1) RT6(+) IELs appear before alpha beta T-cell-receptor-expressin g IELs in diabetes-prone BB, diabetes-resistant BB, and athymic WAG ra ts. 2) In vivo depletion of peripheral RT6(+) T cells in diabetes-resi stant BB rats using a cytotoxic monoclonal antibody is not accompanied by depletion of RT6(+) IELs. 3) A population of RT6(+) T-cell-recepto r-negative IELs is present in normal, euthymic diabetes-resistant BB r ats, constitutes a larger percentage of the euthymic but lymphopenic d iabetes-prone BB mt IEL population, and is the predominant IEL phenoty pe in athymic WAG rats. These results suggest that RT6(+) cells are co mposed of both thymus-dependent and thymus-independent cell subsets th at have different developmental characteristics and may differ in func tion.