Transfer of diabetes in the NOD-scid mouse by CD4 T-cell clones. Differential requirement for CD8 T-cells.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Transfer of diabetes in the NOD-scid mouse by CD4 T-cell clones. Differential requirement for CD8 T-cells.

Diabetes. 1996 Mar;45(3):328-36. Unique Identifier : AIDSLINE MED/96173265
Peterson JD; Haskins K; Department of Immunology, University of Colorado Health Sciences; Center, Denver 80262, USA.

Abstract: Transfer of an interleukin 2/interferon-gamma-secreting islet-specific CD4+ T-cell clone, BDC-6.9, in the immunodeficient NOD-scid mouse induces destruction of pancreatic beta-cells without help from host B-cells, CD4+ T-cells, or CD8+ T-cells. However, a second islet-specific T-cell clone, BDC-2.5, showing the same cytokine profile and T-cell receptor Vbeta expression as BDC-6.9 was not capable of inducing diabetes or insulitis in NOD-scid mice. Even though BDC-2.5 by itself readily induces diabetes in young unmanipulated NOD mice, cotransfer of CD8-enriched T-cells was required to induce disease in NOD-scid mice. Immunohistochemical staining of pancreatic lesions in young NOD mice receiving either BDC-2.5 or BDC-6.9 showed the presence of CD4+, CD8+, Vbeta4+, and MAC-1+ cells within the infiltrate, similar to infiltrates in lesions of spontaneously diabetic female NOD mice. In contrast, NOD- scid mice that received BDC-6.9 showed only the presence of CD4+Vb4+ T-cells and a large population of MAC-1+ cells in islet lesions. NOD-scid recipients of cotransferred BDC- 2.5/CD8+ splenic T-cells showed a small population of CD4+ T-cells and a larger population of CD8+ T-cells within the infiltrated islets, whereas no infiltrate was detectable in recipients of CD8+ splenocytes or BDC-2.5 alone. Our results suggest that at least two types of islet-specific CD4+ T-cell clones play a role in diabetes pathogenesis.

Keywords: Animal Cytoplasmic Granules/PATHOLOGY CD4-Positive T-Lymphocytes/*IMMUNOLOGY/*TRANSPLANTATION CD8-Positive T-Lymphocytes/*IMMUNOLOGY/TRANSPLANTATION Diabetes Mellitus, Insulin-Dependent/*IMMUNOLOGY Flow Cytometry Immunohistochemistry Interferon Type II/SECRETION Interleukin-2/SECRETION Islets of Langerhans/IMMUNOLOGY/PATHOLOGY Mice Mice, Inbred NOD Mice, SCID Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE

960630
M9660712

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