Suppression of concanavalin A-induced responses in splenic lymphocytes by activated macrophages in the non-obese diabetic mouse

Yokono, Koichi; Kawase, Yoshito; Nagata, Masafumi; Hatamori, Nobuo; Baba, Shigeaki

doi:10.1007/bf00265407

Cited by 16 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although it is not known what determines the expression of IL-2R, there are some circumstances that may be responsible for the impaired expression of H-IL-2R in NOD/Shi/Kbe mice. We also reported previously that there are two subpopulations of NOD/Shi/Kbe mice with low and normal IL-2 secretion in our colony (45). Therefore, the low IL-2 production by ConA blasts from NOD mice, reported previously (43), might result in less H-IL-2R expression.…”

Section: Discussionsupporting

confidence: 71%

Impaired Mitogen-Induced Expression of High-Affinity Interleukin 2 Receptors on Spleen Cells From NOD/Shi/Kbe Mice

Hatamori

Yokono²,

Nagata³

et al. 1990

Diabetes

View full text Add to dashboard Cite

The immune abnormalities of NOD mice, a model of human type I (insulin-dependent) diabetes, have been postulated to be T-lymphocyte dependent. We measured responsiveness to exogenous interleukin 2 (IL-2) and IL-2 production in spleen mononuclear cells from female NOD/Shi/Kbe mice after stimulating the cells with concanavalin A (ConA blasts) or phytohemagglutinin (PHA blasts). Exogenous IL-2 produced significantly lower proliferative responses in each blast from 3- and 10-wk-old NOD/Shi/Kbe mice than from control strains. IL-2 production in NOD/Shi/Kbe mice was inclined to decrease but not significantly compared with controls. Even sufficient amounts of recombinant IL-2 (rIL-2) or IL-1 (rIL-1), added with mitogens to the preculture medium, failed to provoke normal proliferative responses from NOD/Shi/Kbe mouse cells. To clarify the reason for this defect, we investigated the expression of IL-2 receptors (IL-2Rs) on mitogen-activated cells with anti-IL-2R monoclonal antibody (PC61) and radiolabeled IL-2. Cytofluorometry showed no significant difference between strains in the number of PC61+ ConA and PHA blasts. However, Scatchard analysis with 125I-labeled IL-2 showed that the number of high-affinity IL-2Rs (H-IL-2Rs), the mediators of the biological activity of IL-2, was decreased in NOD/Shi/Kbe mice compared with controls, whereas the number of low-affinity IL-2Rs (L-IL-2Rs) was not different. Separating the L3T4+ and Lyt-2+ populations of T lymphocytes by cell sorting showed both to be deficient in H-IL-2Rs.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Discussionsupporting

confidence: 71%

Impaired Mitogen-Induced Expression of High-Affinity Interleukin 2 Receptors on Spleen Cells From NOD/Shi/Kbe Mice

Hatamori

Yokono²,

Nagata³

et al. 1990

Diabetes

View full text Add to dashboard Cite

show abstract

“…It has recently been reported that resistance to T-cell apoptosis by deprivation of IL-2 is increased early in the lives of NOD mice (53). Lower production and/or activity of IL-2 in NOD mice may provide a suitable precondition for the expansion of autoreactive T-cells in autoimmune diabetes (52,54,55). Further study on the initial phase of autoimmune diabetes and the role of regulatory T-cells in autoimmune models will reveal the etiology of autoimmune disease and the underlying peripheral tolerance mechanism.…”

Section: Role Of Il-12 In Autoimmune Diabetesmentioning

confidence: 99%

Suppression and acceleration of autoimmune diabetes by neutralization of endogenous interleukin-12 in NOD mice.

et al. 2000

View full text Add to dashboard Cite

A corpus of evidence suggests that T-helper type 1 (Th1)-dependent cellular immunity plays a pivotal role in the pathogenesis of autoimmune diabetes. This study was intended to find ways to prevent the development of NOD diabetes using a neutralizing anti-interleukin (IL)-12 antibody (C17.8) that inhibits Th1 cell differentiation. When C17.8 was administered from 5 to 30 weeks of age, NOD mice exhibited suppression of both insulitis and diabetes. However, when C17.8 administration ceased at 15 weeks of age, 8 of 13 recipients showed diabetes at 30 weeks of age. These results suggest that IL-12 plays an important role not only in the development of effector cells but also in their activation. In contrast, when C17.8 was injected into 2-week-old female NOD mice for 6 consecutive days, all 16 recipients showed diabetes at 30 weeks of age, whereas 12 of 20 control mice became diabetic. This result suggests that depletion of endogenous IL-12 at a young age results in the enhancement of diabetes. Flow cytometric analysis indicated that activated memory T-cells were present in higher numbers after C17.8 treatment. Transfer of spleen cells from 15-week-old C17.8-treated NOD mice to NOD-scid mice resulted in an earlier onset and a higher incidence of diabetes. Furthermore, administration of C17.8 to 2-week-old NOD mice also resulted in a much earlier onset of diabetes. These results suggest that short-term treatment with anti-IL-12 antibody prohibits IL-2 production at a young age, which may influence the expansion and apoptosis of pathogenic T-cells, resulting in the acceleration of autoimmune diabetes.

show abstract

“…In humans at risk for insulin-dependent diabetes mellitus (IDDM), and in the nonobese diabetic (NOD) mouse, defects in APCs contribute to low levels of T-cell activation, poor IL-2 production, and deficient activation of regulatory T cells (9)(10)(11)(12)(13). Such APC defects may predispose to autoimmunity through quantitative reduction in signals required for activation-induced T-cell death (AICD) or regulatory T-cell responses, both of which are important mechanisms for peripheral tolerance (5,14,15).…”

Section: Introductionmentioning

confidence: 99%

“…Monocyte PGS 2 is expressed within 6 hours of activation and then shut off 16 hours after activation (29,30). The proinflammatory PGs (e.g., PGE 2 ), produced in abundance by macrophages and monocytes expressing PGS 2 , are potent modulators of the immune response and tolerance mechanisms (9,(31)(32)(33)(34)(35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus

et al. 1999

View full text Add to dashboard Cite

Prostaglandins (PGs) are lipid molecules that profoundly affect cellular processes including inflammation and immune response. Pathways contributing to PG output are highly regulated in antigen-presenting cells such as macrophages and monocytes, which produce large quantities of these molecules upon activation. In this report, we demonstrate aberrant constitutive expression of the normally inducible cyclooxygenase PG synthase 2 (PGS 2 / COX-2) in nonactivated monocytes of humans with insulin-dependent diabetes mellitus (IDDM) and those with islet autoantibodies at increased risk of developing this disease. Constitutive PGS 2 appears to characterize a high risk for diabetes as it correlates with and predicts a low first-phase insulin response in autoantibody-positive subjects. Abnormal PGS 2 expression in at-risk subjects affected immune response in vitro, as the presence of a specific PGS 2 inhibitor, NS398, significantly increased IL-2 receptor α-chain (CD25) expression on phytohemagglutinin-stimulated T cells. The effect of PGS 2 on CD25 expression was most profound in subjects expressing both DR04 and DQβ0302 high-risk alleles, suggesting that this cyclooxygenase interacts with diabetes-associated MHC class II antigens to limit T-cell activation. These results indicate that constitutive PGS 2 expression in monocytes defines an antigen-presenting cell defect affecting immune response, and that this expression is a novel cell-associated risk marker for IDDM.

show abstract

Suppression of concanavalin A-induced responses in splenic lymphocytes by activated macrophages in the non-obese diabetic mouse

Cited by 16 publications

References 29 publications

Impaired Mitogen-Induced Expression of High-Affinity Interleukin 2 Receptors on Spleen Cells From NOD/Shi/Kbe Mice

Impaired Mitogen-Induced Expression of High-Affinity Interleukin 2 Receptors on Spleen Cells From NOD/Shi/Kbe Mice

Suppression and acceleration of autoimmune diabetes by neutralization of endogenous interleukin-12 in NOD mice.

Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus

Contact Info

Product

Resources

About