Researchers Discover Unique Immune Cell Likely Drives Chronic Inflammation

For the first time, researchers have identified that an immune cell subset called gamma delta T cells may be causing and/or perpetuating the systemic inflammation found with normal aging among the general geriatric population and in HIV-infected people who are responding well to drugs (anti-retrovirals).

Even with effective viral control, HIV-infected individuals are at a higher risk for diseases associated with older age than the general population. Unfortunately, the cell subsets driving inflammation in HIV infection and with normal aging are not yet understood. Also, whether antiretroviral therapy (ART) suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear.

To understand the cellular network that drives the onset and progression of age-associated morbidities in both ART-suppressed HIV and healthy aging, researchers from BUSM conducted a study that measured many markers on the surface of immune cells in the blood of people either with or without HIV that were sub-divided into two groups: younger (less than 35 years) and older (over 50 years) and compared that data with levels of inflammatory proteins in their plasma. This unique group of patients was recruited for the study by co-last author Nina Lin, MD, Assistant Professor of Medicine at BUSM and an infectious disease clinician at Boston Medical Center.

Researchers found that a marker on gamma delta T cells, called TIGIT, tracked significantly with plasma inflammatory markers in both the HIV+ and uninfected subject groups, and therefore could be targeted to potentially stop this ‘inflamm-aging’ found in both HIV+ people and the general geriatric population.

“Our study indicates that a previously uninvestigated immune cell subset in the setting of chronic inflammation with aging or HIV infection, gamma delta T cells, could be causing and/or perpetuating many illnesses in the elderly and in individuals with HIV. Therefore, we believe that targeted gamma delta T cell therapeutics could lead to reduced onset, symptoms, and/or severity of inflammation-related diseases,” explained corresponding author Jennifer Snyder-Cappione, PhD, Assistant Professor of Microbiology and Director of the Flow Cytometry Core Facility at BUSM.

More than 50 percent of the HIV-infected population in the U.S. is older than 50 years and the world’s geriatric population over the ages of 65 and 80 is predicted to double and nearly quadruple, respectively, by 2050. “Revealing and then therapeutically targeting the cell populations and precise immune networks that drive ‘inflamm-aging’ both with and without HIV infection is a preeminent global health priority,” added Dr. Snyder-Cappione.

The researchers, which include first author Anna Belkina, MD, PhD, Assistant Professor of Pathology and Laboratory Medicine at BUSM, hope that their study will spur new investigation and clinical trials targeting gamma delta T cell subsets to control unchecked inflammation and thereby reduce the onset and progression of many chronic diseases.

These findings appear in Frontiers in Immunology.

Funding for this study was provided by the National Institute of Health (R01-DK108056, R01 DA041748-01, R01 AG060890-01, 1UL1TR001430), the National Institute of General Medical Sciences (R44GM117914), and the Army Institute for Collaborative Biotechnologies (W911NF-09-0001).

Editor’s Note:

KD was an employee of Cytobank, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.