Journal
HUMAN IMMUNOLOGY
Volume 69, Issue 11, Pages 781-789Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2008.08.283
Keywords
Rheumatoid arthritis; Systemic lupus erythematosus; CD8 T cells; Regulatory T cells; T-cell based intervention
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Funding
- National Institutes of Health [R01 AR42527, R01 AR41974, R01 A144142, R01 A157266, R01 EY1 1916, R01 AGI 5043]
- American Cellege of Rheumatology
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Rheumatologists have long been focused on developing novel immunotherapeutic agents to manage such prototypic autoimmune diseases as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The ultimate challenge in providing immunosuppressive treatment for patients with RA and SLE has derived from the dilemma that both protective and harmful immune responses result from adaptive immune responses, mediated by highly diverse, antigen-specific T and B cells endowed with powerful effector functions and the ability for long-lasting memory. As regulatory/suppressor T cells can suppress immunity against any antigen, including self-antigens, they emerge as an ideal therapeutic target. Several distinct subtypes of CD8(+) suppressor cells (Ts) have been described that could find application in treating RA or SLE. In a xenograft model of human synovium, CD8(+)CD28(-)CD56(+) T cells effectively suppressed rheumatoid inflammation. Underlying mechanisms involve conditioning of antigen presenting cells (APC). Adoptively transferred CD8(+) T cells characterized by IL-16 secretion have also exhibited disease-inhibitory effects. In mice with polyarthritis, CD8(+) Ts suppressed inflammation by IFN gamma-mediated modulation of the tryptophan metabolism in APC. In SLE animal models, CD8(+) Ts induced by a synthetic peptide exerted suppressive activity mainly via the TGF beta-Foxp3-PD1 pathway. CD8(+) Ts induced by histone peptides were found to downregulate disease activity by secreting TGF beta. In essence, disease-specific approaches may be necessary to identify CD8(+) Ts optimally suited to treat immune dysfunctions in different autoimmune syndromes. (c) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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