Interleukin-2 promotes antigenic reactivity of rested T cells but prolongs the postactivational refractory phase of activated T cells.
IL-2 is a principal autocrine growth factor that promotes T-cell activation and proliferation. However, IL-2 has also been implicated as a key intermediate in the induction and maintenance of self-tolerance in vivo. The purpose of this study was to assess whether the differential regulatory activity of IL-2 was related to the activation status of responder T cells. In cultures of rested myelin basic protein (MBP)-specific T cells, IL-2 not only induced IL-2R alpha but also augmented surface expression of several other activation-associated glycoproteins including OX40, LFA-1, B7.1, B7.2, TCR, and CD4. Pretreatment of T cells with IL-2 also up-regulated subsequent antigen reactivity in assays of MBP-stimulated proliferation and IL-2 production and also promoted proliferative responsiveness to IL-2. In cultures of activated T cells, however, IL-2 inhibited subsequent reactivity to antigen or IL-2 and thereby prolonged a phase of postactivational refractoriness. Exposure of preactivated T cells to IL-2 also inhibited subsequent responses to the mitogenic combination of PMA, ionomycin, and IL-2 without enhancing cell death. These data support the concept that the inhibitory activity of IL-2 is dependent upon the activation status of T cells and is manifest as impaired cell cycle progression in response to a variety of IL-2-dependent stimuli.
Norris
M S
MS
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
McConnell
T J
TJ
Mannie
M D
MD
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002453:Cell Cycle; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D004676:Myelin Basic Protein