Bone marrow is a preferential homing site for autoreactive T-cells in type 1 diabetes.
OBJECTIVE
The pancreatic microenvironment is considered to be the primary location of autoreactive T-cells in type 1 diabetes. Diabetogenic T-cells have also been detected in the spleens of NOD mice. However, it is not known whether bone marrow also contains T-cells specific for self-antigens in hosts with autoimmunity. In this study, we investigated whether autoreactive diabetogenic T-cells are present in the bone marrow of NOD mice.


METHODS
Bone marrow and splenic T-cells of female NOD mice were purified and tested for their cytokine secretion and proliferation in response to stimulation with immunodominant peptides of pancreatic beta-cells. The diabetogenic nature and homing properties of purified bone marrow T-cells were compared with those of splenic T-cells in NOD-Scid and wild-type mice.


RESULTS
The bone marrow T-cells from both hyperglycemic and young euglycemic mice demonstrated profoundly higher proliferation and cytokine production in response to stimulation with beta-cell antigens than T-cells from spleen. Bone marrow T-cells showed rapid expansion and aggressive infiltration into pancreatic islets in NOD-Scid mice and induced hyperglycemia earlier than splenic T-cells. Adoptive transfer of bone marrow T-cells resulted in their trafficking predominantly to bone marrow and pancreatic lymph nodes.


CONCLUSIONS
Our study demonstrates that a large number of diabetogenic T-cells are present in the bone marrow of female NOD mice and that these autoreactive T-cells can be detected long before clinical onset of the disease.
Li
Ruobing
R
Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA.
Perez
Nicolas
N
Karumuthil-Melethil
Subha
S
Vasu
Chenthamarakshan
C
D019264:Adoptive Transfer; D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006943:Hyperglycemia / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010179:Pancreas / Q000473:pathology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines