Functional and genetic analysis of two CD8 T cell subsets defined by the level of CD45RC expression in the rat.
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-gamma 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 F(2)(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.
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.
Emmanuel
E
Xystrakis
Pierre
P
Cavailles
Anne S
AS
Dejean
Bastien
B
Cautain
Céline
C
Colacios
Dominique
D
Lagrange
Marie-Jose
MJ
van de Gaar
Isabelle
I
Bernard
Daniel
D
Gonzalez-Dunia
Jan
J
Damoiseaux
Gilbert J
GJ
Fournié
Abdelhadi
A
Saoudi
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology*; D008297:Male; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D007073:Immunoglobulin E; D017493:Leukocyte Common Antigens