Autor(es):
Leitão, Catarina de Carvalho Soares Dinis, 1980- 
Data: 2008
Identificador Persistente: http://hdl.handle.net/10451/1575
Origem: Repositório da Universidade de Lisboa
Assunto(s): Biologia celular; Teses de doutoramento
Descrição
Tese de doutoramento em Biologia (Biologia Celular), apresentada à Universidade de Lisboa através da Faculdade de Ciências, 2008 In spite of daily T cell production in the thymus associated with intensive proliferation and differentiation of specific T cells upon each antigenic stimulation, peripheral T cells numbers are kept constant. This equilibrium is called homeostasis and subjacent to this process is the concept of competition for limiting resources. Each newly produced T cell has to compete with other new and/or resident peripheral T cell to survive. The periphery comprises two main compartments, the naive and activated/memory T cell pools, for each CD8+ and CD4+ subsets. These compartments are thought to have independent homeostatic regulation, although they share some common resources. The purpose of this thesis is to study the homeostasis of T cells, with a particular interest for the memory subsets, either at steady state or after disruption of this equilibrium upon infection. In the first part of the work, we showed that T cells belonging to different peripheral compartments could compete with each other for p-MHC (peptide-MHC complexes), even if they present a distinct T cell receptor. Moreover, we observed that recognition of p-MHC overlaps not only between different T cell populations but also between T cells ongoing different homeostatic mechanisms such as survival, LDP or accumulation after thymic emigration. In the second part of the study, we show again a modulation of T cell repertoire due to the displacement of memory T cells by BM-derived T cells presenting degenerate TCR. Besides this steady state attrition termed natural attrition , we proposed to study the fate of memory T cells upon Salmonella thymimurium infection. Preliminary data showed that both non-specific CD4+ and CD8+ memory T cells were depleted upon this infection and that type I IFN were not directly implicated in this death. More work remains to be performed to precisely define the targets and mechanism of this attrition.
Tipo de Documento
Tese de Doutoramento
Orientador(es)
Freitas, António A., 1947-; Rodrigues, Maria Gabriela, 1965-
