Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice.
OBJECTIVE
An important prerequisite for the initiation of pancreatic islet inflammation is the recruitment of pathogenic T cells. We investigated the in vivo migration patterns of human islet-reactive T cell clones after transfer into compromised hosts.


METHODS
NOD-scid mice were injected with a mixture of human autoreactive T cells and antigen-presenting cells. Survival and migration of T cells was analysed by fluorescence-activated cell sorter and immunohistochemical analysis of various tissues.


RESULTS
Autoreactive T cells and antigen-presenting cells survived at least 14 days in vivo and accumulated in spleen, pancreatic tissue and pancreas draining lymph nodes, but not elsewhere, as early as 4 days after transfer. This homing was dependent on co-injection of human antigen-presenting cells loaded with autoantigen. Finally, we found that this process is enhanced by streptozotocin treatment. Streptozotocin treatment did not affect the constitutive homing to pancreas draining lymph nodes. Histological analysis of pancreatic tissue sections showed some autoreactive T cells around the islets of Langerhans, comparable to early peri-islet insulitis. However, the majority of pancreas-infiltrating T cells accumulated around blood vessels in the exocrine pancreas. All T cell clones expressed the chemokine receptor CXCR3 that is associated with homing to insulitic lesions in men and mice.


CONCLUSIONS
Our study provides the first evidence of in vivo accumulation in pancreatic tissue of islet-reactive T cells derived from type 1 diabetic patients. The fact that such T cells do not penetrate islets is in line with the concept that additional factors may be required for the entry of T cells into inflamed islets to become diabetogenic.
van Halteren
A G S
AG
Department of Immunohematology and Blood Transfusion, E3Q, LUMC, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Kardol
M J
MJ
Mulder
A
A
Roep
B O
BO
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015788:HLA-A1 Antigen / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010179:Pancreas / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015788:HLA-A1 Antigen