title: T cells in cardiac allograft vasculopathy are skewed to memory Th-1 cells in the presence of a distinct Th-2 population.
abstract: Cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients remains the major complication for long-term survival, due to concentric neointima hyperplasia induced by infiltrating mononuclear cells (MNC). Previously, we showed that activated memory T-helper-1 (Th-1) cells are the major component of infiltrating MNC in coronary arteries with CAV. In this study, a more detailed characterization of the MNC in human coronary arteries with CAV (n = 5) was performed and compared to coronary arteries without CAV (n = 5), by investigating MNC markers (CD1a, DRC-1, CD3, CD20, CD27, CD28, CD56, CD68, CD69, FOXP3 and HLA-DR), cytokines (IL-1A, 2, 4, 10, 12B, IFN-gamma, and TGF-beta1), and chemokine receptors (CCR3, CCR4, CCR5, CCR7, CCR8, CXCR3 and CX3CR1) by immunohistochemical double-labeling and quantitative PCR on mRNA isolated from laser microdissected layers of coronary arteries. T cells in the neointima and adventitia of CAV were skewed toward an activated memory Th-1 phenotype, but in the presence of a distinct Th-2 population. FOXP3 positive T cells were not detected and production of most cytokines was low or absent, except for IFN-gamma, and TGF-beta. This typical composition of T-helper cells and especially production of IFN-gamma and TGF-beta may play an important role in the proliferative CAV reaction.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Hagemeijer
authors.forename: M F M
authors.initials: MF
authors.lastname: van Oosterhout
authors.forename: D F
authors.initials: DF
authors.lastname: van Wichen
authors.forename: J
authors.initials: J
authors.lastname: van Kuik
authors.forename: E
authors.initials: E
authors.lastname: Siera-de Koning
authors.forename: F H J
authors.initials: FH
authors.lastname: Gmelig Meyling
authors.forename: M E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: N
authors.initials: N
authors.lastname: de Jonge
authors.forename: R A
authors.initials: RA
authors.lastname: de Weger
mesh_terms: D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology