PubMed · 10084794
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P Cresswell, J Howard. 1999. Antigen recognition.. https://doi.org/10.1016/s0952-7915(99)80011-9
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Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well-known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-alpha or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.
In an effort to identify tumor-specific antigens recognized by CD4(+) T cells, an approach was developed that allows the screening of an invariant chain-complementary DNA fusion library in a genetically engineered cell line expressing the essential components of the major histocompatibility complex (MHC) class II processing and presentation pathway. This led to the identification of a mutated form of human CDC27, which gave rise to an HLA-DR4-restricted melanoma antigen. A mutated form of triosephosphate isomerase, isolated by a biochemical method, was also identified as an HLA-DR1-restricted antigen. Thus, this approach may be generally applicable to the identification of antigens recognized by CD4(+) T cells, which could aid the development of strategies for the treatment of patients with cancer, autoimmune diseases, or infectious diseases.
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