Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes.
OBJECTIVE
The LEW.1AR1-iddm rat is an animal model of spontaneous type 1 diabetes mellitus. This study analysed how adoptive transfer of selective T cell subpopulations affects the incidence of diabetes.


METHODS
CD4(+) or CD8(+) T cells were isolated from diabetic LEW.1AR1-iddm rats or diabetes-resistant LEW.1AR1 rats. Cells were selectively transferred into athymic LEW.1AR1-Whn ( rnu ) or prediabetic LEW.1AR1-iddm rats. The animals were monitored for blood glucose, islet infiltration and immune cell composition of pancreas-draining lymph nodes.


RESULTS
After adoptive transfer of CD4(+) T cells from diabetic LEW.1AR1-iddm rats into athymic LEW.1AR1-Whn ( rnu ) rats, 50% of the recipients developed diabetes. Transfer of CD8(+) T cells failed to induce diabetes. Only 10% of the athymic recipients became diabetic after co-transfer of CD4(+) and CD8(+) T cells. Adoptive transfer of CD8(+) T cells from LEW.1AR1 or diabetic LEW.1AR1-iddm rats into prediabetic LEW.1AR1-iddm rats significantly reduced the incidence of diabetes. In protected normoglycaemic animals regulatory CD8(+)/CD25(+) and CD4(+)/CD25(+) T cell subpopulations that were also FOXP3-positive accumulated in the pancreas-draining lymph nodes. In this lymphatic organ, gene expression of anti-inflammatory cytokines was significantly higher than in diabetic rats.


CONCLUSIONS
Our results show that adoptive transfer of CD4(+) but not CD8(+) T cells from diabetic LEW.1AR1-iddm rats induced diabetes development. Importantly, CD8(+) T cells from diabetic LEW.1AR1-iddm rats and diabetes-resistant LEW.1AR1 rats provided protection against beta cell destruction. The accumulation of regulatory T cells in the pancreas-draining lymph nodes from protected rats indicates that transferred CD8(+) T cells may have beneficial effects in the control of beta cell autoimmunity.
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
T
T
Arndt
D
D
Wedekind
H
H
Weiss
M
M
Tiedge
S
S
Lenzen
H-J
HJ
Hedrich
A
A
Jörns
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D001786:Blood Glucose; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology*; D010179:Pancreas / Q000276:immunology*; D011236:Prediabetic State / Q000276:immunology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
D001786:Blood Glucose; D016207:Cytokines