Diversity and shape of peripheral effector and regulatory T cell repertoires: validating the Crossregulation model with experimental data
by
Nuno Sepúlveda
Instituto Gulbenkian de Ciência
Coauthors: Jorge Carneiro, Instituto Gulbenkian de Ciência

A healthy immune system involves a fine balance between effector T cells (Teffs) that mount immune responses, and regulatory T cells (Tregs) that suppress them. When this balance is perturbed, immunopathologies arise. Understanding this balance requires to know how diverse are the repertoires of Teffs and Tregs and how they relate to each other. A too large intersection between the repertoires could lead to deleterious inhibition of specific immune responses against harmfull microorganisms, while a too small overlap may open the way to autoimmune responses. Here we address this issue by a Crossregulation model (Immunol. Rev. 216:48-68, 2007) that describes the peripheral dynamics of a large number of clones with both Tregs and Teffs competing for antigen-presenting cells. The model produces different, but testable, predictions for the shape and diversity of peripheral Teff and Treg repertoires: (1) a higher diversity of Teffs than of Tregs, (2) a Lognormal distribution for the clonal size distributions, and (3) a negligible correlation between clonal size distributions. Here we confront these predictions with available experimental data.

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Date received: May 13, 2008