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T cell Maturation and Regulatory T Cell Differentiation:From the Thymus to the Periphery
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Immunological tolerance, that is, the failure to mount an immune response to
an otherwise immunogenic molecule, is one of the fundamental questions in
immunology. The fact that lymphocytes express antigen receptors that are
generated randomly and have the potential to recognize any conceivable
antigen, adds another puzzle to the physiology of immunological tolerance.
The other side of the coin, the general absence of immune responses to self
antigens, is ensured by a tight regulation and several selection steps during
T and B cell differentiation. One of these processes is the differentiation of
regulatory T cells (Treg). While developing in the thymus, T cell clones
bearing receptors with high affinity/avidity to antigens present at the time of
differentiation may be eliminated by apoptosis or, alternatively, express
Foxp3 and become Treg. Treg are key players in the regulation of
immunological tolerance since humans and mice with complete loss of
function variants of this gene develop fatal autoimmune conditions early in
life.(...)
Dissertation presented to obtain the Ph.D degree in Immunology
Dissertation presented to obtain the Ph.D degree in Immunology
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Universidade Nova de Lisboa.Instituto de Tecnologia Química e Biológica