Study reveals functional heterogeneity of CD4 T cells in immune systems

Utilizing a novel transgenic mouse model, Edward Usherwood, PhD of Dartmouth's Norris Cotton Cancer Center and collaborators found that CD4 T cells divide into two different populations that each has a different job. One type performs antiviral functions, and the other survives life in the host. The study, "Functional Heterogeneity in the CD4+ T Cell Response to Murine Y-Herpesvirus 68," was published in the Journal of Immunology.

"The human immune response to viruses and cancer is a complex and multi-pronged effort, but in studies like this one, we are making real progress in understanding how to optimize responses against viruses," explained Usherwood.

Gammaherpesviruses such as the Epstein-Barr virus and the Kaposi's Sarcoma-associated herpesvirus can cause cancer, mostly in immune-suppressed populations such as patients with AIDS. While immune control of these viruses is believed to rely on cytotoxic T cells (CD8 T cells), recent research indicates that helper T cells (CD4 T cells) also play important roles. Research on human patients has shown CD4 T cells that recognize these viruses are present, but it remains unknown to what extent they contribute to control of virus-infected cells.

"In this study, we used a mouse model of gammaherpesvirus infection and performed detailed studies dissecting the exact functions of the CD4 T cells, and how they protect against the virus," said Usherwood. "Using the mouse model and flow cytometry from Dartlab, which is Dartmouth's flow cytometry core facility, allowed a more detailed study of the CD4 T cell response than was possible in previously available approaches."

"The CD4 T cell response represents a relatively tiny population of cells within the host," Usherwood said, noting challenges of the approach. "Identifying and rigorously characterizing these cells was a very challenging, laborious, and costly process. We are fortunate to have high performance flow cytometry here; it is essential to this type of study."

Looking ahead, Usherwood will continue to pursue a particular type of CD4 T cell known as follicular helper CD4 T cells, which appear to be hijacked by Gammaherpesviruses to promote infection, rather than providing protection from infection. Usherwood finds this dichotomy of cells that can either protect from, or collaborate with, the virus to be a fascinating aspect of infections with highly-evolved pathogens like viruses.