In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice.
A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may play a role in the cytotoxicity mediated by CTL that have been primed in vivo. In this study, we investigated the presence of perforin in pancreata from nonobese diabetic (NOD) mice, which have been studied as a model of autoimmune, insulin-dependent (type I) diabetes mellitus. Whereas adult NOD mice spontaneously develop diabetes, it is possible to induce diabetes in young, irradiated NOD mice by adoptive transfer of splenocytes obtained from diabetic donors. By means of immunohistochemical analysis, we were able to detect perforin Ag in a small subpopulation of CD8+/Thy-1+/asialo GM1-/CD4- lymphocytes in the pancreatic islets of animals undergoing both spontaneous and adoptive transfer-mediated insulitis. Perforin+/CD8+ lymphocytes were found in small clusters and were observed to display the morphology of large granular lymphocytes. These observations show for the first time the presence of perforin-containing CD8+ lymphocytes in tissues of animals undergoing autoimmune disease.
Young
L H
LH
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
Peterson
L B
LB
Wicker
L S
LS
Persechini
P M
PM
Young
J D
JD
D000818:Animals; D000918:Antibody Specificity; D000945:Antigens, Differentiation, T-Lymphocyte; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D016827:CD8 Antigens; D002465:Cell Movement; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D007116:Immunization, Passive; D007515:Islets of Langerhans / Q000032:analysis; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000032:analysis* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic / Q000032:analysis* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin