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Taming T cells to ameliorate chikungunya arthritis
Mosquito-borne chikungunya virus causes fever and joint pain; some patients suffer from arthritis for years with no treatment options. In this issue, two studies investigated targeting pathogenic CD4+ T cells to prevent arthritis symptoms in a mouse model of chikungunya virus infection. Teo et al. demonstrated that fingolimod, a drug that sequesters immune cells to lymphoid organs, was able to relieve arthritis symptoms without affecting viral replication. Miner et al. used a combination of abatacept, which blocks T cell costimulation, and a human chikungunya neutralizing antibody to reduce both viral replication and disease severity. Repurposing these clinically available therapies could provide treatment options for chikungunya patients.
In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthritis and can endure for months to years. At present, no approved treatment is effective in preventing or controlling CHIKV infection or disease. We treated mice with eight different disease-modifying antirheumatic drugs and identified CLTA4-Ig (abatacept) and tofacitinib as candidate therapies based on their ability to decrease acute joint swelling. CTLA4-Ig reduced T cell accumulation in the joints of infected animals without affecting viral infection. Whereas monotherapy with CTLA4-Ig or a neutralizing anti-CHIKV human monoclonal antibody provided partial clinical improvement, therapy with both abolished swelling and markedly reduced levels of chemokines, proinflammatory cytokines, and infiltrating leukocytes. Thus, combination CTLA4-Ig and antiviral antibody therapy controls acute CHIKV infection and arthritis and may be a candidate for testing in humans.
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