Human recombinant interferon-beta influences T helper subset differentiation by regulating cytokine secretion pattern and expression of homing receptors.
Type I interferons (IFN) are important regulators of both innate and acquired immunity. We have used an in vitro system of human CD4+ T cell differentiation to determine how IFN-beta influences development of T helper (Th) subsets and homing receptor expression. IFN-beta promoted differentiation of CD4+ T cells that produce low levels of both IFN-gamma and lymphotoxin compared to interleukin (IL)-12-derived Th1 CD4+ T cells. IFN-beta inhibited production of Th2 cytokines (IL-5 and IL-13) and augmented IL-12-mediated IL-10 secretion. In addition, IFN-beta significantly enhanced L-selection expression on CD4+ T cells and synergized with IL-12 to induce expression of cutaneous lymphocyte-associated antigen (CLA). This Th1 L-selectin+, CLA+ phenotype is characteristic of T cells found in normal human skin and suggests a role for type I IFN in the regulation of Th subset differentiation and tissue-specific homing receptors.
McRae
B L
BL
Department of Pathology, Division of Biological Sciences, University of Chicago, IL 60637-1463, USA.
Picker
L J
LJ
van Seventer
G A
GA
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019041:L-Selectin / Q000096:biosynthesis / Q000235:genetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009928:Organ Specificity; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D018793:Interleukin-13; D015848:Interleukin-5; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D011993:Recombinant Fusion Proteins; D019041:L-Selectin; D016753:Interleukin-10; D018664:Interleukin-12; D016899:Interferon-beta