Immature Dendritic Cell Therapy Confers Durable Immune Modulation in an Antigen-Dependent and Antigen-Independent Manner in Nonobese Diabetic Mice.

Dendritic cell (DC) immunotherapy has been effective for prevention of type 1 diabetes (T1D) in NOD mice but fails to protect if initiated after active autoimmunity. As autoreactivity expands inter- and intramolecularly during disease progression, we investigated whether DCs unpulsed or pulsed with cell antigenic dominant determinants (DD), subdominant determinants (SD), and ignored determinants (ID) could prevent T1D in mice with advanced insulitis. We found that diabetes was significantly delayed by DC therapy.

Increased IFN-α-producing plasmacytoid dendritic cells (pDCs) in human Th1-mediated type 1 diabetes: pDCs augment Th1 responses through IFN-α production.

Increasing evidence suggests that type 1 IFN (IFN-αβ) is associated with pathogenesis of Th1-mediated type 1 diabetes (T1D). A major source of IFN-αβ is plasmacytoid dendritic cells (pDCs). In this study, we analyzed peripheral blood pDC numbers and functions in at-risk, new-onset, and established T1D patients and controls.

Dendritic cell deficiency associated with development of BK viremia and nephropathy in renal transplant recipients.

Background: BK virus nephropathy (BKVN) is a significant cause of renal allograft loss. Although overall intensity of immunosuppression is the greatest risk factor, recipient immune factors likely also play a role in the pathogenesis. Dendritic cells (DC) are potent antigen-presenting cells important for the induction of anti-viral cytotoxic T-cell responses.

Rabbit polyclonal mouse antithymocyte globulin administration alters dendritic cell profile and function in NOD mice to suppress diabetogenic responses.

Mouse antithymocyte globulin (mATG) prevents, as well as reverses, type 1 diabetes in NOD mice, through mechanisms involving modulation of the immunoregulatory activities of T lymphocytes. Dendritic cells (DC) play a pivotal role in the generation of T cell responses, including those relevant to the autoreactive T cells enabling type 1 diabetes. As Abs against DC are likely generated during production of mATG, we examined the impact of this preparation on the phenotype and function of DC to elucidate novel mechanisms underlying its beneficial activities.

Apoptotic non-beta cells suppress beta cell antigen-reactive T cells and induce beta cell antigen-specific regulatory T cells.

Steady-state cell apoptosis plays an important role in maintenance of self-tolerance. Based on this notion, the use of apoptotic cells to restore self-tolerance to beta cell antigens is a rational approach to type 1 diabetes (T1D) prevention. Our previous study demonstrated that transfusion of apoptotic beta cells induced immune tolerance to beta cell antigens in NOD mice.

Infusion of UVB-treated splenic stromal cells induces suppression of beta cell antigen-specific T cell responses in NOD mice.

Our previous study has demonstrated that transfusion of UVB-irradiation-induced apoptotic beta cells effectively prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the limitation of beta cell source would preclude the clinical application of this approach. Therefore, in the present study, we have attempted to establish a more practical approach by utilizing apoptotic non-beta cells to prevent T1D.

Transfusion of apoptotic beta-cells induces immune tolerance to beta-cell antigens and prevents type 1 diabetes in NOD mice.

In vivo induction of beta-cell apoptosis has been demonstrated to be effective in preventing type 1 diabetes in NOD mice. Based on the notion that steady-state cell apoptosis is associated with self-tolerance and the need for developing a more practical approach using apoptotic beta-cells to prevent type 1 diabetes, the current study was designed to investigate apoptotic beta-cells induced ex vivo in preventing type 1 diabetes. The NIT-1 cell line serves as a source of beta-cells.

Dendritic cells post-maturation are reprogrammed with heightened IFN-gamma and IL-10.

Mature dendritic cells (mDCs) undergo "exhaustion" in producing cytokines. Nevertheless, whether this "exhaustion" of mDCs is selective to certain cytokines, or whether mDCs have specific cytokine-producing profiles has yet to be defined. Herein, we investigated the cytokine production in vitro by immature DCs (iDCs) and LPS-induced mDCs.

The effects of renal transplantation on peripheral blood dendritic cells.

Recent advances allow accurate quantification of peripheral blood (PB) myeloid and plasmacytoid dendritic cell (DC) populations (mDC and pDC, respectively), although the response to renal transplantation (RT) remains unknown. Using flow cytometry, PBDC levels were quantified in patients with end stage renal disease (ESRD) undergoing RT. PBDC levels were significantly reduced in ESRD patients pre-RT compared to healthy controls, with further reduction noted immediately following a hemodialysis session.

Abnormal peripheral blood dendritic cell populations in type 1 diabetes.

Type 1 diabetes (T1D) is a T cell-mediated disease. Various DC populations play important roles in initiating and directing T cell responses and thus may be critical for T1D pathogenesis. We thus examined peripheral blood DC1 and DC2 populations by flow cytometry in healthy controls, subjects at risk for T1D, new-onset patients, and established T1D patients.

Defective maturation of myeloid dendritic cell (DC) in NOD mice is controlled by IDD10/17/18.

We previously demonstrated that adoptive transfer of NOD pancreatic lymph node (PLN) DC protected recipients from diabetes. Our recent studies showed that the tolerogenic DC population presented islet antigens and were mature myeloid DC that did not produce IL-12, suggestive of exhausted or fully mature DC. Extensive characterization of the DC population in vivo in NOD and control mice demonstrated a specific deficiency of PLN tolerogenic DC in older mice.