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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.

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

12/1989

Volume

143

Pages

3994 - 3999

Addresses

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.

Keywords

Islets of Langerhans, T-Lymphocytes, Cytotoxic, Cells, Cultured, Animals, Mice, Inbred Strains, Mice, Diabetes Mellitus, Experimental, Autoimmune Diseases, Membrane Glycoproteins, Membrane Proteins, Antigens, CD8, Antigens, Differentiation, T-Lymphocyte, Immunization, Passive, Staining and Labeling, Cell Movement, Antibody Specificity, Phenotype, Pore Forming Cytotoxic Proteins, Perforin