The CD8 T Cell in HIV: New Insights from Tissue vs. Blood

For obvious reasons, physicians rely on peripheral blood samples to describe the state of the immune system in an HIV-infected individual, and follow the impact of antiretroviral therapies on activity of the virus and immune function. But new data from a large international collaboration that included amfAR-funded scientist Dr. Steven Deeks, suggest that most prior studies, all involving blood, failed to consider a major component of the body’s attack against HIV: the resident memory CD8 T cell, or CD8 TRM.

 Dr. Steven Deeks

Dr. Steven Deeks

Writing in the June issue of Science Immunology, Dr. Deeks, from the University of California, San Francisco, and colleagues* emphasize that the CD8+ killer T cell is required for effective immune control of HIV. However, this type of immune cell exists in three forms. Only two, the central memory and effector memory T cells, circulate in blood. The third form, TRM, resides in lymphoid and non-lymphoid tissues. Yet these TRM cells establish a front line of defense to eliminate invading viruses and bacteria, and do so largely without involvement of circulating CD8 T cells.

Deeks and associates demonstrate that TRM cells dominate the CD8+ killer T cell response against HIV in lymph nodes and other lymph tissue throughout the body. They obtained tissue samples from HIV-infected individuals in the acute and early stages of infection. The highest frequency of these cells was found in “elite controllers,” individuals who maintain very low levels of HIV in the absence of ART.

This discovery has several implications. Importantly, it is known that the potency of certain experimental vaccines against SIV, the simian form of HIV, in monkeys can be predicted from the magnitude of virus-specific CD8 T cells in the lymph tissue of these animals. Expanding knowledge of the activity of the CD8 TRM cells in these tissues should, as the authors conclude, inform “new approaches to the development of vaccines or immunotherapeutic strategies designed to eliminate the viral reservoir in established HIV infection.” In other words, help us reach a cure.

*From the University of Pennsylvania, the Karolinska Institute in Stockholm, the Instituto Nacional de Enfermedades Respiratorias in Mexico City, the National Institutes of Health, the University of Minnesota, Emory University, Case Western Reserve, and Cardiff University in Wales.

Dr. Laurence is amfAR’s senior scientific consultant.