       Document 0472
 DOCN  M9620472
 TI    Interleukin (IL) 4, in the absence of antigen stimulation, induces an
       anergy-like state in differentiated CD8+ TC1 cells: loss of IL-2
       synthesis and autonomous proliferation but retention of cytotoxicity and
       synthesis of other cytokines.
 DT    9602
 AU    Sad S; Mosmann TR; Department of Medical Microbiology and Immunology,
       University of; Alberta, Edmonton, Canada.
 SO    J Exp Med. 1995 Nov 1;182(5):1505-15. Unique Identifier : AIDSLINE
       MED/96042147
 AB    Naive T cells in the periphery mainly secrete interleukin (IL) 2 upon
       activation. After stimulation in the presence of appropriate
       costimulators, both CD4+ and CD8+ T cells differentiate into effector
       cells secreting distinct T helper (Th) 1- and Th2-like cytokine
       patterns. Subsequent to differentiation, both CD4+ (Th1 and Th2) and
       CD8+ (TC1 and TC2) cells are stable and cannot be induced to
       differentiate into the opposite pattern or revert to the naive cytokine
       secretion pattern. We now show that IL-4 caused committed TC1 bulk
       populations or clones to lose the ability to synthesize IL-2. The cells
       retained the ability to secrete interferon (IFN) gamma,
       granulocyte/macrophage colony-stimulating factor, and tumor necrosis
       factor, did not synthesize any Th2 cytokines, and did not alter cell
       surface marker expression. IL-4 rapidly inhibited IL-2-synthesizing
       ability in the absence or presence of antigen-presenting cells, thus
       demonstrating that IL-4 acted directly on TC1 cells. The defect in IL-2
       synthesis could not be reversed by subsequent stimulation with potent
       antigen-presenting cells in the presence of IL-2 and anti-IL-4, or with
       anti-CD3 plus anti-CD28 antibodies. Both IL-2+ and IL-2- TC1 cells were
       strongly cytotoxic toward allogeneic but not syngeneic targets. However,
       IL-2- TC1 cells were unable to proliferate unless exogenous IL-2 was
       provided. TC1 cells that lose IL-2 synthesis but retain IFN-gamma
       synthesis and cytotoxicity may be similar to the anergic cells induced
       by stimulation of CD4+ or CD8+ cells in the absence of costimulators.
       These results suggest that during a mixed type 1/type 2 response in
       vivo, IL-4 may induce the IL-2+ TC1-->IL-2-TC1 conversion, and thus
       curtail the expansion of the TC1 response without impairing short-term
       effector function.
 DE    Animal  Antigen-Presenting Cells/IMMUNOLOGY  Cell Differentiation/DRUG
       EFFECTS  Cell Division/DRUG EFFECTS  Cells, Cultured  Clonal
       Anergy/*DRUG EFFECTS  Cytotoxicity, Immunologic/DRUG EFFECTS
       CD8-Positive T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY  Female  Gene
       Expression Regulation/DRUG EFFECTS  Granulocyte-Macrophage
       Colony-Stimulating Factor/SECRETION  Interferon Type II/SECRETION
       Interleukin-2/*BIOSYNTHESIS/GENETICS/PHARMACOLOGY
       Interleukin-4/*PHARMACOLOGY  Lymphokines/*SECRETION  Mice  Mice, Inbred
       C57BL  Support, Non-U.S. Gov't  Th1 Cells/DRUG EFFECTS/IMMUNOLOGY  Tumor
       Necrosis Factor/SECRETION  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

