Dendritic cell membrane CD83 enhances immune responses by boosting intracellular calcium release in T lymphocytes

Autor(es)

Pinho, Mariana Pereira ^[1] ; Migliori, Isabella Katz ^[1] ; Flatow, Elizabeth Alexandra ^[1] ; Barbuto, Jose Alexandre M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Leukocyte Biology; v. 95, n. 5, p. 755-762, MAY 2014.
• Citações Web of Science: 12

Resumo

CD83 is a marker of mDCs directly related to their lymphostimulatory ability. Some data suggest that it has a central role in the immune system regulation, but how this function is performed remains to be determined. This work aimed to analyze the influence of CD83, present in mDCs, in the modulation of calcium signaling in T lymphocytes. Mo were differentiated into iDCs and activated with TNF-alpha. iDCs were treated, 4 h before activation, with siRNA(CD83), to reduce CD83 expression. Purified allogeneic T lymphocytes were labeled with the calcium indicator Fluo-4-AM, and calcium mobilization in the presence of mDCs was analyzed. CD83 knockdown mDCs induced lower calcium signal amplitude in T lymphocytes (29.0 +/- 10.0) compared with siRNA(scr)-treated mDCs (45.5 +/- 5.3). In another set of experiments, surface mDC CD83 was blocked with a specific mAb, and again, decreased calcium signaling in T lymphocytes was detected by flow cytometry and microscopy (fluorescence and confocal). In the presence of antibody, the percentage of responding T cells was reduced from 58.14% to 34.29%. As expected, anti-CD83 antibodies also reduced the proliferation of T lymphocytes (as assessed by CFSE dilution). Finally, in the absence of extracellular calcium, CD83 antibodies abrogated T cell signaling induced by allogeneic mDCs, suggesting that the presence of CD83 in mDC membranes enhances T lymphocyte proliferation by boosting calcium release from intracellular stores in these cells. Decreased availability of CD83 on the surface of dendritic cells decreases their ability to induce calcium mobilization in T lymphocytes. (AU)

• Processo FAPESP: 11/01082-5 - Análise dos papéis da molécula de membrana CD83 na biologia da resposta imune.
• Beneficiário: Mariana Pereira Pinho
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 09/54599-5 - Células dendríticas: elementos integrados do sistema imune - enfoque aplicado
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Modalidade de apoio: Auxílio à Pesquisa - Temático