Tc17 CD8+ T cells potentiate Th1-mediated autoimmune diabetes in a mouse model.
An increase in IL-17-producing CD8+ T (Tc17) cells has been reported in the peripheral blood of children with recent onset type 1 diabetes (T1D), but their contribution to disease pathogenesis is still unknown. To directly study the pathogenic potential of β cell-specific Tc17 cells, we used an experimental model of T1D based on the expression of the neo-self Ag hemagglutinin (HA) in the β cells of the pancreas. When transferred alone, the IL-17-producing HA-specific CD8+ T cells homed to the pancreatic lymph nodes without causing any pancreatic infiltration or tissue destruction. When transferred together with small numbers of diabetogenic HA-specific CD4+ T cells, a strikingly different phenotype developed. Under these conditions, Tc17 cells sustained disease progression, driving the destruction of β-islet cells, causing hyperglycemia and ultimately death. Disease progression did not correlate with functional or numerical alterations among the HA-specific CD4+ T cells. Rather, the transferred CD8+ T cells accumulated in the pancreatic islets and a considerable fraction converted, under the control of IL-12, to an IFN-γ-producing phenotype. Our data indicate that Tc17 cells are not diabetogenic but can potentiate a Th1-mediated disease. Plasticity of the Tc17 lineage is associated with transition to overt disease in this experimental model of T1D.
INSERM, Unité 1043, F-31300 Toulouse, France.
Amit
A
Saxena
Sabine
S
Desbois
Nadège
N
Carrié
Myriam
M
Lawand
Lennart T
LT
Mars
Roland S
RS
Liblau
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D015854:Up-Regulation / Q000276:immunology
D020381:Interleukin-17; D007371:Interferon-gamma