title: Impaired in vivo CD4+ T cell expansion and differentiation in aged mice is not solely due to T cell defects: decreased stimulation by aged dendritic cells.
abstract: CD4+ T cells regulate humoral and cell-mediated immune responses, which are progressively impaired in aging, resulting in susceptibility to infections and cancer. Dendritic cells (DCs) are major activators of T cells, providing signals that drive their expansion and differentiation. In this study, we asked if decreased CD4+ T cell responses were influenced by the age of DCs rather than being exclusively due to T cell defects. Old T cells transferred to young recipients expanded and differentiated similarly to young T cells. However, aged recipients were poor stimulators of both old and young T cells, which failed to acquire CD44 expression and produce interferon gamma (IFN-γ). DCs in aged hosts expressed fewer MHC-peptide complexes. The CD86 expression in the DCs of both hosts was similar; however, CD40 levels were reduced in old DCs. Finally, old DCs failed to produce inflammatory cytokines in response to LPS. Our results indicate that the impairment of aged CD4+ T cell function is intimately related to multiple alterations in aged DCs, rather than being caused solely by intrinsic T cell defects, suggesting that the function of aged T cells may be partially rescued in vivo when appropriate stimulation is applied. These findings are relevant to vaccination design for elderly populations.
authors: Departamento de Biologia Celular e Molecular (FABIO) and Instituto de Pesquisas Biomédicas, PUCRS, Av. Ipiranga, Porto Alegre, RS, Brazil.
authors: Luciana F
authors: LF
authors: Pereira
authors: Ana Paula Duarte
authors: AP
authors: de Souza
authors: Thiago J
authors: TJ
authors: Borges
authors: Cristina
authors: C
authors: Bonorino
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D018960:Hyaluronan Receptors; D008070:Lipopolysaccharides; D010455:Peptides; D007371:Interferon-gamma