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Functional and Genetic Analysis of Two CD8 T Cell Subsets Defined by the Level of CD45RC Expression in the Rat¹

Emmanuel Xystrakis^2,*, Pierre Cavailles^2,*, Anne S. Dejean^*, Bastien Cautain^3,*, Céline Colacios^*, Dominique Lagrange^*, Marie-Jose van de Gaar, Isabelle Bernard^*, Daniel Gonzalez-Dunia^*, Jan Damoiseaux, Gilbert J. Fournié^* and Abdelhadi Saoudi^4,*

^* Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 563, Institut Fédératif de Recherche (IFR) 30, Hôpital Purpan and Université Paul Sabatier, Toulouse, France; and Department of Immunology, University Maastricht, Maastricht, The Netherlands

Differential cytokine production by T cells plays an important role in the outcome of the immune response. We show that the level of CD45RC expression differentiates rat CD8 T cells in two subpopulations, CD45RC^high and CD45RC^low, that have different cytokine profiles and functions. Upon in vitro stimulation, in an Ag-presenting cell-independent system, CD45RC^high CD8 T cells produce IL-2 and IFN- while CD45RC^low CD8 T cells produce IL-4, IL-10, and IL-13. In vitro, these subsets also exhibit different cytotoxic and suppressive functions. The CD45RC^high/CD45RC^low CD8 T cell ratio was determined in Lewis (LEW) and Brown-Norway (BN) rats. These two rat strains differ with respect to the Th1/Th2 polarization of their immune responses and to their susceptibility to develop distinct immune diseases. The CD45RC^high/CD45RC^low CD8 T cell ratio is higher in LEW than in BN rats, and this difference is dependent on hemopoietic cells. Linkage analysis in a F₂(LEW x BN) intercross identified two quantitative trait loci on chromosomes 9 and 20 controlling the CD45RC^high/CD45RC^low CD8 T cell ratio. This genetic control was confirmed in congenic rats. The region on chromosome 9 was narrowed down to a 1.2-cM interval that was found to also control the IgE response in a model of Th2-mediated disorder. Identification of genes that control the CD45RC^high/CD45RC^low CD8 T cell subsets in these regions could be of great interest for the understanding of the pathophysiology of immune-mediated diseases.

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				R. Dawes, S. Petrova, Z. Liu, D. Wraith, P. C. L. Beverley, and E. Z. Tchilian Combinations of CD45 Isoforms Are Crucial for Immune Function and Disease J. Immunol., March 15, 2006; 176(6): 3417 - 3425. [Abstract] [Full Text] [PDF]