Targeted depletion of lymphotoxin-alpha-expressing TH1 and TH17 cells inhibits autoimmune disease - PubMed (original) (raw)
doi: 10.1038/nm.1984. Epub 2009 Jun 28.
Ganesh A Kolumam, Xin Yu, Michelle Francesco, Sinisa Ivelja, Ivan Peng, Peter Gribling, Jean Shu, Wyne P Lee, Canio J Refino, Mercedesz Balazs, Andres Paler-Martinez, Allen Nguyen, Judy Young, Kai H Barck, Richard A D Carano, Ron Ferrando, Lauri Diehl, Devavani Chatterjea, Jane L Grogan
Affiliations
- PMID: 19561618
- DOI: 10.1038/nm.1984
Targeted depletion of lymphotoxin-alpha-expressing TH1 and TH17 cells inhibits autoimmune disease
Eugene Y Chiang et al. Nat Med. 2009 Jul.
Abstract
Uncontrolled T helper type 1 (T(H)1) and T(H)17 cells are associated with autoimmune responses. We identify surface lymphotoxin-alpha (LT-alpha) as common to T(H)0, T(H)1 and T(H)17 cells and employ a unique strategy to target these subsets using a depleting monoclonal antibody (mAb) directed to surface LT-alpha. Depleting LT-alpha-specific mAb inhibited T cell-mediated models of delayed-type hypersensitivity and experimental autoimmune encephalomyelitis. In collagen-induced arthritis (CIA), preventive and therapeutic administration of LT-alpha-specific mAb inhibited disease, and immunoablated T cells expressing interleukin-17 (IL-17), interferon-gamma and tumor necrosis factor-alpha (TNF-alpha), whereas decoy lymphotoxin-beta receptor (LT-betaR) fusion protein had no effect. A mutation in the Fc tail, rendering the antibody incapable of Fcgamma receptor binding and antibody-dependent cellular cytotoxicity activity, abolished all in vivo effects. Efficacy in CIA was preceded by a loss of rheumatoid-associated cytokines IL-6, IL-1beta and TNF-alpha within joints. These data indicate that depleting LT-alpha-expressing lymphocytes with LT-alpha-specific mAb may be beneficial in the treatment of autoimmune disease.
Comment in
- Targeting lymphotoxin depletes pathogenic T cells.
Hansen AM, Caspi RR. Hansen AM, et al. Nat Med. 2009 Jul;15(7):732-3. doi: 10.1038/nm0709-732. Nat Med. 2009. PMID: 19584860 Free PMC article. - Lymphotoxin-alpha: another (and better?) therapeutic target in autoimmune disease?
Aggarwal A. Aggarwal A. Natl Med J India. 2009 Nov-Dec;22(6):307-8. Natl Med J India. 2009. PMID: 20384020 No abstract available.
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