PMID- 8871045
OWN - NLM
STAT- MEDLINE
DCOM- 19970122
LR  - 20171116
IS  - 0904-1850 (Print)
IS  - 0904-1850 (Linking)
VI  - 22
DP  - 1996 Aug
TI  - Modulation of the human IgE response.
PG  - 58s-62s
AB  - Studies on the immunological basis of allergic diseases have indicated that 
      enhanced production of the cytokines interleukin (IL)-4 and IL-13 and the reduced 
      production of interferon-gamma (IFN-gamma) by allergen-specific T-cells 
      contribute to enhanced immunoglobulin E (IgE) synthesis and the development of 
      allergic disease in certain individuals. Therefore, inhibition of IL-4 and IL-13 
      synthesis or blocking of activities of these cytokines would be one approach to 
      inhibiting IgE production. In the present communication, novel approaches toward 
      this goal are discussed. It is shown that an IL-4 mutant protein, in which the 
      tyrosine residue at position 124 is replaced by aspartic acid (IL-4,Y124D), binds 
      with high affinity to the IL-4 receptor, without receptor activation. IL-4,Y124D 
      acts as a potent antagonist both of IL-4 and IL-13 activity in vitro, and 
      inhibits immunoglobulin G4 (IgG4) and IgE production induced by these cytokines. 
      These data are compatible with the notion that the IL-4 and IL-13 receptors are 
      complex receptors, which share a common component, which is required for signal 
      transduction. In addition, it has been demonstrated that allergen-specific 
      T-cells, belonging to the T-helper 2 (Th2) subset can be rendered anergic after 
      incubation with allergen-derived peptides representing minimal T-cell activation 
      inducing epitopes. These anergic Th2 cells failed to produce IL-4 and IL-13, and 
      failed to proliferate after activation with allergen and antigen-presenting cells 
      (APC). The anergized T cells also failed to give B-cells help in IgE synthesis, 
      although they expressed normal levels of the CD40 ligand (CD40L). Exogenous IL-4 
      and IL-13 failed to restore IgE synthesis, indicating that in addition to CD40L 
      other co-stimulatory signals are required for productive T-cell/B-cell 
      interactions, resulting in IgE synthesis. IgE production was restored by 
      exogenous IL-2, demonstrating that IL-2 reverses the nonresponsive state and 
      helper function of these nonresponsive T-cells. It is tempting to speculate that 
      induction of T-cell nonresponsiveness by allergen-derived peptides may represent 
      the underlying mechanisms for successful immunotherapy in allergenic patients.
FAU - de Vries, J E
AU  - de Vries JE
AD  - Human Immunology Dept, DNAX Research Institute for Molecular and Cellular 
      Biology, Palo Alto, CA, USA.
FAU - Yssel, H
AU  - Yssel H
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Eur Respir J Suppl
JT  - The European respiratory journal. Supplement
JID - 8910681
RN  - 0 (CD40 Antigens)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-13)
RN  - 0 (Recombinant Proteins)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD40 Antigens/immunology
MH  - Humans
MH  - Hypersensitivity/*immunology
MH  - Immune Tolerance
MH  - Immunodominant Epitopes/immunology
MH  - Immunoglobulin E/*biosynthesis/physiology
MH  - Immunoglobulin G/biosynthesis
MH  - Immunotherapy
MH  - Interleukin-13/antagonists & inhibitors/biosynthesis/immunology
MH  - Interleukin-4/antagonists & inhibitors/biosynthesis/immunology
MH  - Mice
MH  - Mice, SCID
MH  - Recombinant Proteins/immunology
MH  - T-Lymphocytes/*physiology
MH  - Th2 Cells/immunology
RF  - 35
EDAT- 1996/08/01 00:00
MHDA- 1996/08/01 00:01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 1996/08/01 00:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
PST - ppublish
SO  - Eur Respir J Suppl. 1996 Aug;22:58s-62s.