scholarly journals Determinant Spreading of  T Helper Cell 2 (Th2) Responses to Pancreatic Islet Autoantigens

1997 ◽  
Vol 186 (12) ◽  
pp. 2039-2043 ◽  
Author(s):  
Jide Tian ◽  
Paul V. Lehmann ◽  
Daniel L. Kaufman
Keyword(s):  
Nod Mice ◽  
Insulin Dependent Diabetes Mellitus ◽  
T Cell Response ◽  
Autoimmune Response ◽  
Dependent Diabetes Mellitus ◽  
Autoreactive T Cell ◽  
Th2 Responses ◽  
Infectious Tolerance ◽  
Insulin Dependent ◽  
Cellular And Humoral Immunity

The nature (Th1 versus Th2) and dynamics of the autoimmune response during the development of insulin-dependent diabetes mellitus (IDDM) and after immunotherapy are unclear. Here, we show in nonobese diabetic (NOD) mice that the autoreactive T cell response starts and spreads as a pure Th1 type autoimmunity, suggesting that a spontaneous Th1 cascade underlies disease progression. Surprisingly, induction of antiinflammatory Th2 responses to a single β cell antigen (βCA) resulted in the spreading of Th2 cellular and humoral immunity to unrelated βCAs in an infectious manner and protection from IDDM. The data suggest that both Th1 and Th2 autoimmunity evolve in amplificatory cascades by generating site-specific, but not antigen-specific, positive feedback circuits. Determinant spreading of Th2 responses may be a fundamental mechanism underlying antigen-based immunotherapeutics, explaining observations of infectious tolerance and providing a new theoretical framework for therapeutic intervention.

scholarly journals T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice.

1989 ◽  
Vol 169 (5) ◽  
pp. 1669-1680 ◽  
Author(s):  
C Boitard ◽  
R Yasunami ◽  
M Dardenne ◽  
J F Bach
Keyword(s):  
T Cells ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Insulin Dependent Diabetes Mellitus ◽  
Lymphoid Cells ◽  
Dependent Diabetes Mellitus ◽  
Spleen Cells ◽  
Nonobese Diabetic ◽  
Insulin Dependent ◽  
Onset Of Diabetes

The nonobese diabetic (NOD) mouse has recently been introduced as a model for insulin-dependent diabetes mellitus. The role of regulatory T cells in the development of antipancreatic autoimmunity in this model remains unclear. To evaluate the presence of suppressive phenomena, we used disease transfer by spleen cells from diabetic NOD mice into preirradiated adult recipients as a model for accelerated disease. Suppressor phenomena were detected by testing the protection afforded by lymphoid cells from nondiabetic NOD mice against diabetes transfer in irradiated recipients. Transfer of diabetes was delayed by reconstituting recipients with spleen cells from nondiabetic NOD donors. The greatest protection against diabetes transfer was conferred by spleen cells from 8-wk-old nondiabetic female NOD mice. Depletion experiments showed that the protection was dependent on CD4+ cells. Protection was also detected within thymic cells from nondiabetic NOD mice and protection conferred by spleen cells was abrogated by thymectomy of nondiabetic female, but not male, NOD donors at 3 wk of age. These findings indicate that suppressive CD4+ T cells that are dependent on the presence of the thymus may delay the onset of diabetes in female diabetes-prone NOD mice.

scholarly journals Cellular and humoral immunity of diabetics at the early stages of the disease development: experience gained in the treatment with azathioprin, an immunosuppressant

1993 ◽  
Vol 39 (1) ◽  
pp. 3-7
Author(s):  
I. I. Dedov ◽  
I. A. Abugova ◽  
P. I. Shishko ◽  
M. Sh. Shamkhalova
Keyword(s):  
Diabetes Mellitus ◽  
Humoral Immunity ◽  
Complement Activation ◽  
Reference Group ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Early Stages ◽  
Insulin Dependent ◽  
Cellular And Humoral Immunity

A total of 40 patients with type 1 diabetes mellitus, in whom the disease was diagnosed 1 to 12 months previously, were examined. An imbalance between the T and В cellular components of the immunity was found in the patients with the early stages of the disease, as was an elevated titer of the complement Cl component as against the reference group. The degree of the immunologic shifts was in direct correlation with the HLA A9 antigen expression, this relationship being the most marked in cases with the HLA DR3 and DR4. The incidence of these antigens expression was significantly higher in the patients with marked immunity shifts, than in those with negligible immunity changes. Therapy with an immunosuppressant azathioprin was associated with a noticeable reduction of the initially elevated cellular immunity parameters (total T and В lymphocyte counts, T helpers-inductors, DR carriers) and a trend towards a reduction of all the components and total activity of the classical route of the complement activation predominantly at the expense of the Cl and C5 components. The efficacy of this drug in therapy of new cases of insulin-dependent diabetes mellitus was confirmed, and the undisputable relationship between the efficacy of immunity suppression, that helped achieve a clinical remission, and the disease duration, was demonstrated. Monitoring of the cellular and humoral immunity parameters, of the activity of the classical route of the complement activation permitted an indirect judgement on the usefulness of immunity suppression for the correction of immunity disorders as factors contributing to the development of microvascular disturbances in insulin-dependent diabetes mellitus.

scholarly journals Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence.

1990 ◽  
Vol 171 (6) ◽  
pp. 2077-2089 ◽  
Author(s):  
M B Oldstone
Keyword(s):  
Diabetes Mellitus ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Insulin Dependent Diabetes Mellitus ◽  
Lymphocytic Infiltration ◽  
Lymphocytic Choriomeningitis ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Beta Cell Destruction ◽  
Insulin Dependent

A situation in which virus can be used as a therapeutic agent to prevent a lethal autoimmune disease is explored. Nonobese insulin-dependent diabetes (NOD) mice spontaneously develop insulin-dependent diabetes mellitus (IDDM), characterized by lymphocytic infiltration into the islets of Langerhans and beta cell destruction, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. Infection of NOD mice with lymphocytic choriomeningitis virus (LCMV) aborts the autoimmune manifestations and resultant IDDM. The viruses' effect is on a subset of CD4+ lymphocytes. Ablating this autoimmune diabetes does not significantly alter immune responses to a variety of non-LCMV antigens that require CD4+ lymphocyte participation. The prevention of IDDM associated with viral therapy is maintained throughout the life spans of NOD mice.

scholarly journals α/β–T Cell Receptor (TCR)+CD4−CD8− (NKT) Thymocytes Prevent Insulin-dependent Diabetes Mellitus in Nonobese Diabetic (NOD)/Lt Mice by the Influence of Interleukin (IL)-4 and/or IL-10

1998 ◽  
Vol 187 (7) ◽  
pp. 1047-1056 ◽  
Author(s):  
Kirsten J.L. Hammond ◽  
Lynn D. Poulton ◽  
Linda J. Palmisano ◽  
Pablo A. Silveira ◽  
Dale I. Godfrey ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cell ◽  
T Cell Receptor ◽  
Nod Mice ◽  
Insulin Dependent Diabetes Mellitus ◽  
Cell Receptor ◽  
Nkt Cells ◽  
Dependent Diabetes Mellitus ◽  
Nonobese Diabetic ◽  
Insulin Dependent

We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in α/β-T cell receptor (TCR)+CD4−CD8− NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM in NOD mice was studied by the infusion of thymocyte subsets into young female NOD mice. A single intravenous injection of 106 CD4−/lowCD8− or CD4−CD8− thymocytes from female (BALB/c × NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. Insulitis was still present in some recipient mice, although the cell infiltrates were principally periductal and periislet, rather than the intraislet pattern characteristic of insulitis in unmanipulated NOD mice. Protection was not associated with the induction of “allogenic tolerance” or systemic autoimmunity. Accelerated IDDM occurs after injection of splenocytes from NOD donors into irradiated adult NOD recipients. When α/β-TCR+ and α/β-TCR− subsets of CD4−CD8− thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the α/β-TCR+ population was protective, confirming that NKT cells were responsible for this activity. The protective effect in the induced model of IDDM was neutralized by anti–IL-4 and anti–IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. These results have significant implications for the pathogenesis and potential prevention of IDDM in humans.

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