Homeostasis of the T cell memory compartment

• Author(s): Leitão, Catarina de Carvalho Soares Dinis, 1980-
• Date: 2008
• Persistent ID: http://hdl.handle.net/10451/1575
• Origin: Repositório da Universidade de Lisboa
• Subject(s): Biologia celular; Teses de doutoramento
• Document Type: Doctoral thesis
• Language: English
• Advisor(s): Freitas, António A., 1947-; Rodrigues, Maria Gabriela, 1965-
• Contributor(s): Repositório da Universidade de Lisboa

Description

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.

Fundação para a Ciência e a Tecnologia, (FCT), (bolsa de referência SFRH/BD/16762/2004)