PMID- 9618517
OWN - NLM
STAT- MEDLINE
DCOM- 19980709
LR  - 20230331
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 95
IP  - 12
DP  - 1998 Jun 9
TI  - Differential expression of major histocompatibility complex class II genes on 
      murine macrophages associated with T cell cytokine profile and 
      protective/suppressive effects.
PG  - 6936-40
AB  - Protective/suppressive major histocompatibility complex (MHC) class II alleles 
      have been identified in humans and mice where they exert a disease-protective and 
      immunosuppressive effect. Various modes of action have been proposed, among them 
      differential expression of MHC class II genes in different types of 
      antigen-presenting cells impacting on the T helper type 1 (Th1)-Th2 balance. To 
      test this possibility, the expression of H-2 molecules from the four haplotypes 
      H-2(b), H-2(d), H-2(k), and H-2(q) was determined on bone marrow-derived 
      macrophages (BMDMs) and splenic B cells. The I-Ab and I-Ek molecules, both well 
      characterized as protective/suppressive, are expressed at a high level on almost 
      all CD11b+ BMDMs for 5-8 days, after which expression slowly declines. In 
      contrast, I-Ad, I-Ak, and I-Aq expression is lower, peaks over a shorter period, 
      and declines more rapidly. No differential expression could be detected on B 
      cells. In addition, the differential MHC class II expression found on macrophages 
      skews the cytokine response of T cells as shown by an in vitro restimulation 
      assay with BMDMs as antigen-presenting cells. The results indicate that 
      macrophages of the protective/suppressive haplotypes express MHC class II 
      molecules at a high level and exert Th1 bias, whereas low-level expression favors 
      a Th2 response. We suggest that the extent of expression of the class II gene 
      gates the back signal from T cells and in this way controls the activity of 
      macrophages. This effect mediated by polymorphic nonexon segments of MHC class II 
      genes may play a role in determining disease susceptibility in humans and mice.
FAU - Baumgart, M
AU  - Baumgart M
AD  - Deutsches Rheuma ForschungsZentrum, Monbijoustrasse 2, D-10117 Berlin, Germany.
FAU - Moos, V
AU  - Moos V
FAU - Schuhbauer, D
AU  - Schuhbauer D
FAU - Muller, B
AU  - Muller B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cytokines/immunology
MH  - Gene Expression Regulation/*immunology
MH  - Histocompatibility Antigens Class II/*genetics/*immunology
MH  - Lymphocyte Activation
MH  - Macrophage Activation
MH  - Macrophages/*immunology
MH  - Mice
MH  - Th1 Cells/*immunology
MH  - Th2 Cells/*immunology
PMC - PMC22692
EDAT- 1998/06/17 00:00
MHDA- 1998/06/17 00:01
PMCR- 1998/12/09
CRDT- 1998/06/17 00:00
PHST- 1998/06/17 00:00 [pubmed]
PHST- 1998/06/17 00:01 [medline]
PHST- 1998/06/17 00:00 [entrez]
PHST- 1998/12/09 00:00 [pmc-release]
AID - 1161 [pii]
AID - 10.1073/pnas.95.12.6936 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6936-40. doi: 
      10.1073/pnas.95.12.6936.