An evolving autoimmune microenvironment regulates the quality of effector T cell restimulation and function.
Proc Natl Acad Sci U S A
; 111(25): 9223-8, 2014 Jun 24.
Article
en En
| MEDLINE
| ID: mdl-24927530
ABSTRACT
Defining the processes of autoimmune attack of tissues is important for inhibiting continued tissue destruction. In type 1 diabetes, it is not known how cytotoxic effector T cell responses evolve over time in the pancreatic islets targeted for destruction. We used two-photon microscopy of live, intact, individual islets to investigate how progression of islet infiltration altered the behavior of infiltrating islet-specific CD8(+) T cells. During early-islet infiltration, T-cell interactions with CD11c(+) antigen-presenting cells (APCs) were stable and real-time imaging of T cell receptor (TCR) clustering provided evidence of TCR recognition in these stable contacts. Early T cell-APC encounters supported production of IFN-γ by T effectors, and T cells at this stage also killed islet APCs. At later stages of infiltration, T-cell motility accelerated, and cytokine production was lost despite the presence of higher numbers of infiltrating APCs that were able to trigger T-cell signaling in vitro. Using timed introduction of effector T cells, we demonstrate that elements of the autoimmune-tissue microenvironment control the dynamics of autoantigen recognition by T cells and their resulting pathogenic effector functions.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Comunicación Celular
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Linfocitos T CD8-positivos
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Diabetes Mellitus Tipo 1
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Microambiente Celular
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Células Presentadoras de Antígenos
Límite:
Animals
Idioma:
En
Año:
2014
Tipo del documento:
Article