title: Quantitating effector and regulatory T lymphocytes in immune responses by limiting dilution analysis modeling.
abstract: Although there is currently no doubt that regulatory lymphocytes represent a master player in the immune system, a major unresolved problem is the accurate quantitation of these cells among unfractionated cell populations. This difficulty mainly arises because there are no specific immunophenotypic markers that can reliably discriminate between effector and regulatory lymphocytes. To face this problem, we have developed computational models of limiting dilution analyses addressing the question of the accurate estimation of the frequencies of effector and regulatory cells functionally engaged in an immune response. A set of generic equations were provided to form a framework for modeling limiting dilution data, enabling discrimination between qualitatively different models of suppression. These models include either one or two subpopulations of regulatory cells, featured by either low or potent regulatory activity. The potential of this modeling approach was illustrated by the accurate determination of the frequencies of effector and regulatory T lymphocytes in one real limiting dilution experiment of CD4+ CD25+ T lymphocytes performed in the context of an allogeneic response in the human system. The crucial advantage of the limiting dilution method over the "static, phenotype-based" method is the dynamic evaluation of effector and regulatory T cell biology through their actual functional activity.
authors.affiliation: Institut National de la Santé de la Recherche Médicale U353, Institut Albert Bonniot, Université Joseph-Fourier, CHRU Grenoble, Fédération d'Onco-Hématologie, Hopital Michallon, Grenoble, France. Thierry.Bonnefoix@ujf-grenoble.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Bonnefoix
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnefoix
authors.forename: Pascal
authors.initials: P
authors.lastname: Perron
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Mi
authors.forename: Wan Fai
authors.initials: WF
authors.lastname: Ng
authors.forename: Robert
authors.initials: R
authors.lastname: Lechler
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Bensa
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007158:Immunologic Techniques; D016013:Likelihood Functions; D018655:Lymphocyte Count / Q000379:methods; D018448:Models, Immunological; D016012:Poisson Distribution; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012044:Regression Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015375:Receptors, Interleukin-2