Abnormalities of T cell activation in the rheumatoid synovium detected with monoclonal antibodies to CD3.
The chronic inflammation of rheumatoid arthritis (RA) is associated with hypofunction of synovial fluid (SF) T cells. We studied the mechanisms leading to this abnormality using a mitogenic monoclonal antibody specific for the T cell receptor-associated CD3 complex. We found that SF cells are defective in their response to anti-CD3 antibodies as measured by proliferation, generation of natural cytotoxicity, and induction of the Tac (p55) component of the IL2 receptor. Nevertheless, these cells do bear functional IL2 receptors and are more responsive to IL2 than are resting peripheral blood T cells. In searching for a mechanism to explain the reduced IL2 production, we found that polyamines (whose oxidation products can down-regulate proliferation and IL2 production) are elevated in RA cells from both blood and SF. We postulate that the chronic activation of RA T cells triggers this feedback loop which constitutes a defensive mechanism aimed at reducing the T cell driven autoimmune and inflammatory process.
Talal
N
N
Clinical Immunology Section, Audie L. Murphy Memorial Veterans Hospital, San Antonio, TX.
Tovar
Z
Z
Dauphinee
M J
MJ
Flescher
E
E
Dang
H
H
Galarza
D
D
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D011073:Polyamines / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011073:Polyamines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2