Researchers at La Jolla Institute for Immunology are working to understand how a viral infection like chikungunya (CHIKV) can cause persistent joint pain that closely resembles rheumatoid arthritis.
Their research suggested CD4+ T cells that step up to fight the virus caused chronic inflammation in the process (Cell Reports Med 2025;6[5]:102134).
They studied immune cells found in blood samples from a group of chikungunya patients and found CD4+ T cells showed a strong response to CHIKV. Although CD4+ T cells are a normal part of the body’s immune response, they are almost always accompanied by CD8+ killer T cells. Yet, the CD4+ T cells were most active in fighting CHIKV. The researchers found that 87% of patients had detectable levels of CHIKV-specific memory CD4+ T cells in their blood six years after their initial infection. In contrast, only 13% of patients still had CHIKV-specific memory CD8+ T cells in their blood after six years.
According to La Jolla's Daniela Weiskopf, PhD, this kind of CD4+ T-cell profile is more commonly seen in patients with autoimmune diseases. This CD4+ T-cell activity may help explain the association between CHIKV infection and chronic, autoimmune-like disease.
Normally, CD4+ T cells are “polyfunctional,” but CHIKV patients who developed severe joint pain had more monofunctional CD4+ T cells. Even years after initial infection, their T cells primarily produced tumor necrosis factor (TNF)-alpha, which helps direct immune cell activity during an infection, but TNF-alpha is not supposed to linger long after a virus has been cleared.
The new study offers evidence that these monofunctional CD4+ T cells may be the culprits behind joint pain and chronic inflammation after CHIKV infection, they said.
This article is from the June 2025 print issue.