Researchers find immune system molecule that could lead to TB vaccine

A research team led by scientists from the University of Pittsburgh recently determined that the presence of a particular immune system molecule effectively prevented tuberculosis of the lungs from becoming active and deadly.

The National Institutes of Health-funded study researched human and animal TB-infected cells. The researchers examined the clusters of immune cells that surround infected lung cells.

"A hallmark of TB that we see on chest X-rays is the granuloma, a collection of immune cells that surround the infected lung cells," Shabaana A. Khader, the study's senior author, said. "But what we didn't know was the difference between a functioning protective granuloma, as in latent TB, and a non-protective granuloma seen in active TB patients. We aimed to find immunologic markers that could show us the status of the infection."

The scientists found that granulomas containing ectopic lymphoid structures were associated with effective TB suppression. The immune cells, known as T cells, had a surface marker called CXCR5 that was associated with the presence of the ectopic lymphoid structures.

"The presence of CXCR5 provides a specific address for the infected cells that tells the immune cells where to focus their attention to contain the problem," Khader said. "That results in the formation of ectopic lymphoid structures and the protective granuloma that keeps TB infection under control, unlike in active disease. Without CXCR5, those structures did not form and active TB was more likely."

When the researchers delivered the CXCR5 T cells from donor animals to TB-infected mice without CXCR5, the ectopic structure formation was restored, enabling decreased TB susceptibility.

"The protective power of CXCR5 points us in a novel direction for future management of TB," Khader said. "These findings have powerful implications for the development of vaccines to prevent infection."

More than two billion people worldwide are infected with TB-causing Mycobacterium tuberculosis.

The study, conducted by researchers at the University of Pittsburgh School of Medicine and the Children's Hospital at the University of Pittsburgh Medical Center, was published in Wednesday's online edition of the Journal of Clinical Investigation.

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