PMID- 17313444
OWN - NLM
STAT- MEDLINE
DCOM- 20070529
LR  - 20220310
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 121
IP  - 1
DP  - 2007 May
TI  - CTLA-4 regulates allergen response by modulating GATA-3 protein level per cell.
PG  - 62-70
AB  - T helper type 2 (Th2) cell differentiation requires the expression of GATA-3, a 
      transcription factor that allows transcriptional activation of Th2 cytokine genes 
      through chromatin remodelling. We investigated the role of the negative 
      costimulatory receptor cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the 
      regulation of GATA-3 expression, Th2 differentiation and immunoglobulin 
      production during the immune response to allergens. BALB/c mice were immunized 
      with a recombinant major allergenic component of Parietaria judaica pollen, rPar 
      j I, and treated with blocking anti-CTLA-4 or control antibodies. Results showed 
      that in vivo CTLA-4 blockade enhanced the Par j I-specific immunoglobulin E (IgE) 
      serum level. In contrast, Par j I-specific IgG2a serum level was reduced, 
      suggesting that CTLA-4 blockade skewed immunoglobulin production towards 
      interleukin-4 (IL-4) -dependent immunoglobulin isotypes. Consistently, CTLA-4 
      blockade increased the frequency of Par j I-specific Th2 cells but not Th1 cells, 
      as well as IL-4 and IL-5 but not interferon-gamma production. Our data also 
      showed that CTLA-4 blockade enhanced the GATA-3 : T-bet messenger RNA ratio. 
      Interestingly, in vivo CTLA-4 blockade did not increase the frequency of GATA-3 
      protein-expressing cells. In contrast, it enhances GATA-3 protein level per cell. 
      Further, in vitro results show that the anti-CTLA-4 monoclonal antibody, by 
      competing with CD80 for CTLA-4 binding, induced an enhancement in the frequency 
      of IL-4-producing cells that correlates with the increase in GATA-3 protein level 
      per cell. In conclusion, CTLA-4, by affecting the level of GATA-3 per cell, 
      contributes to keeping this factor under the threshold required to become a Th2 
      effector cell. Consequently, it affects IgE/IgG2a production and contributes to 
      the outcome of allergen-specific immune responses.
FAU - Nasta, Francesca
AU  - Nasta F
AD  - ENEA, Unit of Biotechnology, Section of Toxicology and Biomedicine, Rome, Italy.
FAU - Corinti, Silvia
AU  - Corinti S
FAU - Bonura, Angela
AU  - Bonura A
FAU - Colombo, Paolo
AU  - Colombo P
FAU - Di Felice, Gabriella
AU  - Di Felice G
FAU - Pioli, Claudio
AU  - Pioli C
LA  - eng
PT  - Journal Article
DEP - 20070220
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Allergens)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Ctla4 protein, mouse)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (Gata3 protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Par j I protein, Parietaria judaica)
RN  - 0 (Plant Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Allergens/*immunology
MH  - Animals
MH  - Antibodies, Monoclonal/immunology
MH  - Antigens, CD/*immunology
MH  - Antigens, Differentiation/*immunology
MH  - CTLA-4 Antigen
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Female
MH  - GATA3 Transcription Factor/genetics/*metabolism
MH  - Gene Expression Regulation/immunology
MH  - Immunoglobulin E/biosynthesis
MH  - Immunoglobulin G/biosynthesis
MH  - Interleukin-4/biosynthesis
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Plant Proteins/immunology
MH  - RNA, Messenger/genetics
MH  - Recombinant Proteins/immunology
MH  - Th2 Cells/immunology
PMC - PMC2265929
EDAT- 2007/02/23 09:00
MHDA- 2007/05/30 09:00
PMCR- 2008/05/01
CRDT- 2007/02/23 09:00
PHST- 2007/02/23 09:00 [pubmed]
PHST- 2007/05/30 09:00 [medline]
PHST- 2007/02/23 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - IMM2537 [pii]
AID - 10.1111/j.1365-2567.2007.02537.x [doi]
PST - ppublish
SO  - Immunology. 2007 May;121(1):62-70. doi: 10.1111/j.1365-2567.2007.02537.x. Epub 
      2007 Feb 20.