Ontogeny and immunohistochemical localization of thymus-dependent and thymus-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 insulin-dependent diabetes mellitus. Diabetes-resistant BB rats have normal numbers of RT6+ T cells, and insulin-dependent diabetes mellitus can 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 generate RT6+ intestinal epithelial lymphocytes (IELs). The goal of these studies was to analyze the ontogeny of RT6+ IELs and peripheral lymphoid cells by in situ immunohistochemistry. We observed the following. 1) RT6+ IELs appear before alpha(beta) T-cell-receptor- expressing IELs in diabetes-prone BB, diabetes-resistant BB, and athymic WAG rats. 2) In vivo depletion of peripheral RT6+ T cells in diabetes-resistant BB rats using a cytotoxic monoclonal antibody is not accompanied by depletion of RT6+ IELs. 3) A population of RT6+ T-cell-receptor-negative IELs is present in normal, euthymic diabetes-resistant BB rats, constitutes a larger percentage of the euthymic but lymphopenic diabetes-prone BB rat IEL population, and is the predominant IEL phenotype in athymic WAG rats. These results suggest that RT6+ cells are composed of both thymus-dependent and thymus-independent cell subsets that have different developmental characteristics and may differ in function.
Waite
D J
DJ
Department of Medicine, Diabetes Division, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, USA.
Appel
M C
MC
Handler
E S
ES
Mordes
J P
JP
Rossini
A A
AA
Greiner
D L
DL
D036002:ADP Ribose Transferases; D000818:Animals; D000831:Animals, Newborn; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000032:analysis*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB; D011923:Rats, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000254:growth & development
D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D007518:Isoantibodies; D008562:Membrane Glycoproteins; C079330:RT6.1 antibody; D016693:Receptors, Antigen, T-Cell, alpha-beta; D036002:ADP Ribose Transferases; C090163:Art2b protein, rat