Splenic macrophages from the NOD mouse are defective in the ability to present antigen

Piganelli, Jon D.; Martin, Tracy; Haskins, Katherine

doi:10.2337/diabetes.47.8.1212

Cited by 21 publications

(12 citation statements)

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“…Previous dissection of this proliferative phenotype within the NOD immune system had indicated that the CD4 T cell compartment was intrinsically normal when confronted with stimuli that did not require interaction with other cell types [21,22,231. In light of these data, we considered the possibility that this antibody therapy might not mediate its effect solely by action on the T cell compartment, for were that the complete mechanism, NOD mice might be receptive to its effects.…”

Section: Contact With Alloantigens In the Presence Of Anti-cd45rb Leamentioning

confidence: 99%

Resistance to anti-CD45RB-induced tolerance in NOD mice: mechanisms involved

et al. 2004

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While great advances have been made in the success of islet transplantation to cure autoimmune diabetes, this protocol remains limited by our inability to induce donor-specific tolerance within the recipient. The profound resistance of the NOD mouse to tolerance-inducing regimens that are routinely successful in other strains further defines the imposing barriers that must be surmounted. Herein, we have assessed the utility of anti-CD45RB therapy to induce tolerance to allografts in C57BL/6 and NOD-strain mice. We find that, as with other therapies, NOD mice are also resistant to this manipulation, despite robust tolerance induction in the comparison strain. Analysis of cell surface markers revealed a number of changes within the B lymphocyte compartment following contact with antibody and alloantigen in the B6 strain. The absence of reciprocal changes within the NOD lymphocyte compartment suggests that B cells might contribute to the mechanism of action of this therapy and to the resistance to immunological tolerance noted in the NOD strain.

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Section: Contact With Alloantigens In the Presence Of Anti-cd45rb Leamentioning

confidence: 99%

Resistance to anti-CD45RB-induced tolerance in NOD mice: mechanisms involved

et al. 2004

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“…Defective maturation of macrophages and of DC has been described in NOD mice [28, 29], and in type 1 diabetes patients [30]. This is correlated with a reduced ability of antigen presentation by NOD mouse APC [31] and may lead to the inefficient induction of negative selection in the thymus, and/or to the impaired activation of peripheral regulatory T cells.…”

Section: Introductionmentioning

confidence: 99%

Fibronectin Receptor Defects in NOD Mouse Leucocytes: Possible Consequences for Type 1 Diabetes

et al. 2004

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Integrins of the very late antigen (VLA) family mediate leucocyte traffic to lymphoid organs under physiological conditions and in chronic inflammatory situations such as autoimmunity. Accordingly, the current thinking is of a positive correlation between VLA expression and capability of the generation of autoimmunity. Herein we discuss recent findings on the defective expression of integrin-type fibronectin receptors a4b1 (VLA-4) and a5b1 (VLA-5) in the non-obese diabetic (NOD) mouse, a murine model of autoimmune insulindependent diabetes mellitus. As compared with normal animals, NOD thymocytes (including the CD4 þ CD25 þ regulatory T cells) exhibit a decrease in the membrane expression of a5b1, resulting in a functional impairment of fibronectin-mediated interactions, including cell migration. Interestingly, thymocytes that are trapped within the giant perivascular spaces seen in NOD thymus are consistently a5b1 negative, suggesting that the progressive arrest of mature cells can be related to the a5b1 defect. Peripheral T cells also exhibit decreased a5b1 membrane expression and impaired fibronectin-driven migration. Additionally, we observed a defect in a4b1 fibronectin receptor expression in NOD macrophages. Peritoneal, bone marrow-derived-precursor, as well as thymic macrophages of NOD mice showed an impaired upregulation of a4-integrin chain expression, dependent on the level of macrophage maturation. Overall these data lead to the notion that NOD leucocytes bear distinct fibronectin receptormediated cell migration defects, which may be involved in the pathogenesis and/or pathophysiology of the autoimmune events seen in NOD mice. Further studies will be helpful to define whether or not this concept can be applied for other autoimmune diseases.

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“…Thus, T-regs can continue to prevent autoreactivity from becoming systemic while permitting relaxation of this protection in local regions where there may be injury or infection. These data also indicate how dysregulation of APC activation, migration, and antigen presentation (to T-regs and naive T cells) can lead to autoimmune disease by counter-regulating T-regs in inappropriate locations (22, 23). Additionally, this interpretation may provide insight into other models of autoimmunity in which infection is thought to trigger disease.…”

Section: Discussionmentioning

confidence: 82%

Regulatory T-Cell Counter-Regulation by Innate Immunity Is a Barrier to Transplantation Tolerance

Kim

Lee

Moore

et al. 2009

American Journal of Transplantation

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Innate immune signals foster adaptive immunity through activation of antigen-presenting cells. Recent in vitro evidence suggests that innate signaling may also contribute to immunity by countering the effects of regulatory T cells (T-regs), counter-regulation. We present in vivo evidence using a transgenic skin allograft model that the function of T-regs is lost in the setting of acute skin transplantation but remains intact when grafts were transplanted 1 month prior to allow surgery-induced inflammation to abate. Our findings identify T-reg counter-regulation as a naturally occurring process that accompanies transplantation and an important barrier to T-reg-mediated tolerance. Our finding further highlights the central role of regulatory cell deactivation in the initiation of the immune response.

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Splenic macrophages from the NOD mouse are defective in the ability to present antigen

Cited by 21 publications

References 0 publications

Resistance to anti-CD45RB-induced tolerance in NOD mice: mechanisms involved

Resistance to anti-CD45RB-induced tolerance in NOD mice: mechanisms involved

Fibronectin Receptor Defects in NOD Mouse Leucocytes: Possible Consequences for Type 1 Diabetes

Regulatory T-Cell Counter-Regulation by Innate Immunity Is a Barrier to Transplantation Tolerance

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