Transfer of diabetes in the NOD-scid mouse by CD4 T-cell clones. Differential requirement for CD8 T-cells.
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.
Peterson
J D
JD
Department of Immunology, University of Colorado Health Sciences Center, Denver 80262, USA.
Haskins
K
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003594:Cytoplasmic Granules / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID
D007376:Interleukin-2; D007371:Interferon-gamma