       Document 0517
 DOCN  M9620517
 TI    Peptide-induced anergy in allergen-specific human Th2 cells results in
       lack of cytokine production and B cell help for IgE synthesis. Reversal
       by IL-2, not by IL-4 or IL-13.
 DT    9602
 AU    Fasler S; Aversa G; Terr A; Thestrup-Pedersen K; de Vries JE; Yssel H;
       Human Immunology Department, DNAX Research Institute for; Molecular and
       Cellular Biology, Palo Alto, CA 94304, USA.
 SO    J Immunol. 1995 Nov 1;155(9):4199-206. Unique Identifier : AIDSLINE
       MED/96025875
 AB    The induction of anergy in T cells is believed to be the result of
       triggering of the TCR in the absence of adequate costimulation mediated
       through the interaction of CD28 and its ligands, CD80 and CD86. Here, we
       demonstrate that stimulation of human group I allergen in
       Dermatophagoides pteronyssinus extract (Der p 1)-specific CD4+ Th2-like
       T cell clones with Der p 1-derived peptides in the absence of
       professional APC results in a state of nonresponsiveness. The induction
       of anergy occurred despite the expression of high levels of CD28, CD80,
       and CD86 on the surface of the T cell clones and was not prevented by
       the addition of anti-CD28 mAb. The anergic, Der p 1-specific, Th2 cells
       failed to mobilize calcium from intracellular stores, to proliferate,
       and to produce IL-2, IL-4, IL-13, GM-CSF, and TNF-alpha following
       optimal stimulation with Der p 1-derived peptide and autologous APC.
       However, they mobilized intracellular calcium following stimulation with
       Ca(2+)-ionophore and produced all of the above cytokines, including
       IFN-gamma, when stimulated with phorbol ester and Ca2+ ionophore. These
       results indicate that the anergic T cell clones are capable of
       responding to signals circumventing the TCR/CD3 complex activation
       pathway. In contrast to T cell clones optimally activated with peptide
       and APC, anergic T cells failed to induce IgG4 and IgE synthesis when
       cocultured with B cells, even in the presence of exogenous IL-4 or
       IL-13. Anergic T cells expressed normal levels of CD40L, suggesting that
       their inability to help in Ig production by B cells is due to conditions
       other than a lack of expression of this molecule. Finally, exogenous
       IL-2 restored the helper function of anergic Th2 T cells for IgE
       production by B cells, which was greatly enhanced by the addition of
       IL-4 or IL-13. These data suggest that induction of anergy in
       allergen-specific Th2 T cells by allergen-derived peptides may play an
       important role in the successful desensitization of allergic patients.
 DE    Allergens/IMMUNOLOGY  B-Lymphocytes/IMMUNOLOGY  Clonal
       Anergy/*IMMUNOLOGY  Clone Cells  Cytokines/*BIOSYNTHESIS/PHYSIOLOGY
       Down-Regulation (Physiology)/IMMUNOLOGY  Epitopes
       Glycoproteins/IMMUNOLOGY  Human  IgE/*BIOSYNTHESIS  IgG/BIOSYNTHESIS
       Immunophenotyping  Interleukin-13/BIOSYNTHESIS/PHYSIOLOGY
       Interleukin-2/BIOSYNTHESIS/PHYSIOLOGY
       Interleukin-4/BIOSYNTHESIS/PHYSIOLOGY  Interleukins/*PHYSIOLOGY
       *Lymphocyte Cooperation  Receptor-CD3 Complex, Antigen, T-Cell/ANALYSIS
       Th2 Cells/*IMMUNOLOGY  JOURNAL ARTICLE

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

