INVESTIGADORES
GENARO Ana Maria
artículos
Título:
Impaired immune responses in streptozotocin-induced type I diabetes in mice.
Autor/es:
ROXANA RUBINSTEIN; ANA MARÍA GENARO; ALICIA B MOTTA; GRACIELA A CREMASCHI; MIRIAM WALD
Revista:
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Editorial:
Blackwell Scientific Publications
Referencias:
Año: 2008 vol. 154 p. 235 - 246
ISSN:
0009-9104
Resumen:
Summary Diabetes is widely believed to predispose to serious infections. However, the mechanisms linking diabetes and immunosuppression are not well defined. One potential mediator of the altered defense mechanisms is hyperglycemia. It has been identified as the main factor contributing to the development of diseases associated to diabetes mellitus. In this study we analyze the immune response in diabetes and the direct effect of hyperglycemia on T and B lymphocyte reactivity. Diabetes induced an early decrease in IgG levels in the secondary response. However, both primary responses against a T-cell-dependent or independent antigen were affected after 6 months of diabetes induction. T- and B- cell proliferation was only decreased at this time. To gain insight into the potential mechanisms involved, we evaluated the influence of hyperglycemia over the immune response. Pre-incubation of lymph node and spleen cells in a high glucose (HG) containing medium lead to a significant time and dose dependent decrease in T- and B-cell proliferation. This effect was associated to the presence of HG-derived supernatants. Still viable cells after HG exposition were able to improve their proliferative response when cultured with the mitogen in a fresh standard medium. HG diminished cell viability, increased apoptosis and induced oxidative stress in lymphocytes. These results indicate that HG concentrations can directly affect lymphoid cell growth. An increase in oxidative stress would be implicated in this deleterious effect. The possibility that prolonged exposure to pathologically HG concentrations would result in the immunosuppressive state observed in diabetes is also discussed.