T-cell regulation in RA

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Curr Opin Rheumatol. 2004 May;16(3):212-7.

T-cell regulation in rheumatoid arthritis.

Goronzy JJ, Weyand CM.

Lowance Center for Human Immunology, Emory University School of

Medicine, Atlanta, Georgia, USA.

PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is characterized by a

chronic T-cell response that has escaped normal control mechanisms. This

review summarizes recent insights in pathways that are functional in RA

and that favor continuous and pathogenic T-cell activation. RECENT

FINDINGS: T-cell activation is ultimately determined by positive signals

from costimulatory molecules and negative signals from regulatory T

cells. Blockade of the classic costimulatory pathway, CD28-CD80 or CD86,

is beneficial in RA. Additional pathways that predominantly control the

activation of memory and effector T cells are functionally important in

synovial inflammation. Some of these costimulatory molecules (such as

stimulatory killer cell immunoglobulin-like receptors and NKG2D) appear

to be relatively specific for RA and not to play a role in normal immune

responses. In addition to this predominance of positive signals,

age-disproportionate decline in thymic activity in RA may lead to a

diminution of regulatory T cells and loss of their negative signals.

SUMMARY: The successful treatment trial of RA with CTLA-4Ig clearly

documents the importance of T-cell costimulation in RA disease activity.

Novel costimulatory pathways may be of even greater significance than

CD28 in RA and may represent promising new therapeutic targets. The

finding of reduced thymic activity in RA is exciting and will stimulate

further studies of T-cell homeostasis and the function of regulatory

cells.

PMID: 15103247

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Mayo Clinic in Rochester

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s Hopkins Medicine

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