Biomedical subjects

Caroline Aspord

Publications and source records attributed to Caroline Aspord.

4 recordsLinked to original sources

PubMed2005

T-cell homing to the pancreas in autoimmune mouse models of diabetes: in vivo MR imaging.

PURPOSE: To evaluate the efficiency of T-cell labeling with anionic magnetic nanoparticles (AMNPs) and in vivo magnetic resonance (MR) imaging monitoring of T-cell homing to the pancreas. MATERIALS AND METHODS: In vivo MR images of pancreas were obtained with a 7-T MR system in 12 NOD (nonobese diabetic) mice at 11 and 20 days after injection of AMNP-loaded or unloaded T cells. Homing of loaded T cells in pancreatic lymph nodes was detected by the presence of a focal dark spot with T2* effect in a caudal area of the pancreas. Detection of loaded T cells in pancreatic islets was evaluated by comparison of histograms of MR signal intensity generated in whole pancreas in mice injected with loaded and unloaded T cells. Homing of loaded T cells was confirmed at transmission electronic microscopy (TEM). Fifty-six mice underwent all experiments. RESULTS: Focal dark spots with T2* effect were observed at 11 days in all three mice injected with loaded T cells and in none of the three mice injected with unloaded T cells. At 20 days, a more diffuse negative enhancement of the whole pancreas was noticed in one mouse injected with loaded T cells than in three mice injected with unloaded T cells. Presence of loaded T cells was confirmed with TEM. In vitro and in vivo tests confirmed that survival and function were not altered by loading. CONCLUSION: The ability of MR imaging to depict cell homing in living organisms at least 20 days after cell labeling was demonstrated, opening the way of follow-up in autoimmune diseases and cell therapy.

Animals↗

PubMed2005

Immunotherapy via dendritic cells.

The immune system evolved to protect us from microbes. The antigen (Ag)-nonspecific innate immunity and Ag-specific adaptive immunity synergize to eradicate the invading pathogen through cells, such as dendritic cells (DCZ7) and lymphocytes, and through their effector proteins including antimicrobial peptides, complement, and antibodies. Its intrinsic complexity renders the immune system prone to dysfunction including cancer, autoimmunity, chronic inflammation and allergy. DCs are unique in their capacity to induce and regulate immune responses and are therefore attractive candidates for immunotherapy. However, DCs consist of distinct subsets with common as well as unique functions that lead to distinct types of immune responses. Therefore, understanding DC heterogeneity and their role in immunopathology is critical to design better strategies for immunotherapy. Indeed, what we learn from studying autoimmunity will help us induce strong vaccine specific immunity, either protective, as in the case of microbes, or therapeutic, as in the case of tumors.

Animals↗

PubMed2004

Early events in islets and pancreatic lymph nodes in autoimmune diabetes.

The specific contributions of islet cell microenvironment during the development of autoimmune type 1 diabetes remain unclear. The aims of this study were to identify early immune-driven abnormalities in islets and pancreatic lymph nodes of NOD mice by cDNA arrays. We compared gene expression profiles of purified islets and pancreatic lymph nodes of 4-week-old NOD mice to NOD-SCID and BALB/c mice. To further characterize the networks implicated in beta-cell destruction, we also performed a time-course analysis using islets and pancreatic lymph nodes of NOD mice from 2 to 25 weeks of age. We found consistent changes by cDNA arrays and RT-PCR analyses among islet genes before the detection of CD3+ T cells in the islet periphery associated with dendritic cell attraction, lymphocyte homing, and apoptosis. In contrast to IL-1, TYNFSF13B and osteopontin genes which were specifically activated, the immunoregulatory cytokine IL-11 was poorly detected in NOD islets and pancreatic lymph nodes. Genes involved in angiogenesis were also specifically activated in NOD islets of 2 and 4 weeks of age. The present time-course macroarray and RT-PCR analyses provides a detailed picture of the different genes involved in autoimmune diabetes and illustrates the importance of islet cell microenvironment that prepares the late beta-cell destruction.

Age Factors↗

PubMed2002

alpha4 integrins and L-selectin differently orchestrate T-cell activity during diabetes prevention following oral administration of CTB-insulin.

Oral administration of insulin conjugated to the B chain of cholera toxin (CTB-insulin) in non-obese diabetic (NOD) mice results in diabetes prevention. We investigated the respective contributions of L-selectin (CD62L) and alpha4-integrin pathways during CTB-driven tolerance. Purified CD62L+CD4+ cells from CTB-insulin fed mice significantly reduced the capacity of diabetogenic T cells to transfer diabetes in syngeneic recipients. In vivo antibody blockade of fed animals during adoptive co-transfer experiments indicated that both CD62L and alpha4-integrins pathways were necessary to develop a protective response after oral tolerance induction. In contrast, when antibodies were given to recipient mice, only CD62L was critical for the protection. In vitro stimulated CD62L+CD4+ cells from the spleen of fed animals secreted lower amounts of IL-4 and IL-10 but comparable levels of TGFbeta than CD62L-cells. A reduced IFN-gamma production between the two cell subsets was specifically observed in CTB-insulin fed mice. Furthermore, antibody treatments induced changes in T-cell migration to the spleen, mesenteric and pancreatic lymph nodes. The protective effect was also associated with migration of regulatory T cells into pancreatic islets. Taken together, our results suggest that L-selectin and alpha4-integrin have distinct but complementary roles in the generation and function of regulatory CD4+ T cells following CTB-insulin administration.

Adjuvants, Immunologic↗