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Persistent Viral Infections and T-Cell Repertoires in Older Adults
In older adults, persistent infections caused by herpes viruses can be a common problem. These viruses usually enter the hosts, cause primary disease earlier in life, and remain latent in various cell types. Under the appropriate conditions, these viruses may reactivate to cause disease and elicit recall responses from the adaptive immune system, resulting in inflammation and proliferation of antigen-specific T-cells aimed at suppressing viral replication.
Reactivation of the herpes viruses is more common in immunosuppressed or immunocompromised people who have impaired T-cell immunity, such as transplant recipients and patients infected with the human immunodeficiency virus (HIV).
Human cytomegalovirus (CMV) infects more than 80 percent of adults 60 years and older in the United States. After an acute infection that may produce anywhere from no symptoms in young healthy adults to severe congenital syndromes in newborns, CMV remains latent in mononuclear cells, among other cell types, in a nonreplicating or slowly replicating form.
In immunocompromised patients, CMV is the most common opportunistic pathogen to cause significant morbidity and mortality, reactivating frequently and producing severe disease. However, the long-term clinical effect of CMV infection in people with a competent immune system is not well known. Cardiovascular disease has been associated with CMV seropositivity in adults.
In a recent study involving participants from the Women’s Health and Aging Studies, Johns Hopkins researchers showed for the first time that CMV seropositivity leads to a higher five-year mortality in immunocompetent older women, and that women with the highest CMV IgG antibody concentrations are at the highest mortality risk.
Employing novel technologies in T-cell repertoire analysis, researchers in the Division of Geriatric Medicine and Gerontology are dissecting the T-cell response to CMV infection in order to better understand the basis of its pathogenesis in older adults. Given the changes in T-cell repertoire diversity with aging, these research endeavors will also provide important insights into immune protection in older age and influence strategies to improve vaccine effectiveness in older adults.
Current research studies
- Antigen-specific T-cell receptor repertoires in humans
Sean Leng, MD, PhD
George C. Wang, MD