Assessment of chemokine receptor expression by human Th1 and Th2 cells in vitro and in vivo

• Published in: Journal of leukocyte biology Vol. 65; no. 5; pp. 691 - 699
• Main Authors: Annunziato, Francesco, Cosmi, Lorenzo, Galli, Grazia, Beltrame, Chiara, Romagnani, Paola, Manetti, Roberto, Romagnani, Sergio, Maggi, Enrico
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.05.1999
• Subjects: AIDS/HIV; CCR3; CCR5; CD30; Clone Cells; Crohn Disease - immunology; Crohn Disease - metabolism; CXCR3; CXCR4; Down-Regulation - drug effects; Flow Cytometry; Humans; Immunologic Memory; Interferon-gamma - biosynthesis; Interferon-gamma - pharmacology; Interferon-gamma - physiology; Interleukin-12 - pharmacology; Interleukin-4 - biosynthesis; Interleukin-4 - pharmacology; Interleukin-4 - physiology; LAG‐3; Lymphocyte Activation; Organ Specificity; Receptors, Chemokine - biosynthesis; Th1 Cells - metabolism; Th2 Cells - metabolism; Up-Regulation - drug effects
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.65.5.691

The preferential association of some chemokine receptors with human Th1 or Th2 cells has recently been reported. In this study, the expression of CCR3, CCR5, CXCR3, and CXCR4 were analyzed by flow cytometry in three distinct in vitro models of Th1/Th2 polarization, activated naive and memory T cells, and T‐cell clones, in which the intracellular synthesis of interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) and the surface expression of CD30 and LAG‐3 were also assessed. Moreover, by using immunohistochemistry the in vivo expression of CCR3, CCR5, CXCR3, and CXCR4 was examined in the gut of patients suffering from Crohn's disease, a Th1‐dominated disorder, and in the skin of patients suffering from systemic sclerosis, a Th2‐dominated disorder. CCR5 and LAG‐3 exhibited the same pathway of Th1 association, whereas CXCR3 did not discriminate between Th1‐ and Th2‐dominated responses. On the other hand, CCR3 was found only occasionally in a small proportion of allergen‐specific memory T cells with Th2/Th0 profile of cytokine production in vitro. However, it was neither seen in Th2‐polarized activated naive T cells nor in established Th2 clones and could be detected in vivo only on non‐T cells. Finally, whereas CXCR4 expression was not limited to Th2 cells in vivo, it was markedly up‐regulated by IL‐4 and down‐regulated by IFN‐γ in vitro. Thus, the results of this study confirm the existence of flexible programs of chemokine receptor expression during the development of Th1 and Th2 cells. However, caution is advised in interpreting these receptors as surrogate markers of a given type of effector response. J. Leukoc. Biol. 65: 691–699; 1999.