Analysis of leukocytes recruited to the pancreas by diabetogenic T cell clones.
To investigate host leukocytes recruited to the pancreas by diabetogenic T cells, we administered islet-specific CD4(+) T cell clones to 2-week-old nonobese diabetic (NOD) mice and examined the resulting pancreatic infiltrate by flow cytometry. Two different Vbeta4(+)CD4(+) T cell clones, BDC 2.5 and BDC 6.9, were found to recruit a heterogeneous T cell population as determined by staining with a panel of anti-TCR Vbeta monoclonal antibodies. The majority of the diabetes-initiating, Vbeta4(+) T cell clones migrated to the spleen whereas only 5-8% of the T cell population infiltrating the pancreas was Vbeta4(+). Anti-IL-2 receptor staining indicated that fewer than 10% of the total population of infiltrating lymphocytes within the pancreas were in a highly activated state. We have further found that normal splenic T cells from the NOD mouse proliferate poorly to IL-2 in vitro, yet secrete IFN-gamma in response to IL-2 stimulation. These results suggest that the recruited host T cells in our disease transfer system are not directly pathogenic but, rather, are responding to the small numbers of inflammatory T cell clones by providing cytokines that facilitate the disease process.
Peterson
J D
JD
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, 80262, USA.
Berg
R
R
Piganelli
J D
JD
Poulin
M
M
Haskins
K
K
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma