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.