Th16 - Effects of Cytomegalovirus on T Cell Differentiation in Two Distinct Immunosuppressed Populations

Infection with cytomegalovirus (CMV) induces remodeling of the immune system. Though healthy immunity controls CMV infection, the virus establishes latency and can periodically reactivate. Immunosuppressive drugs impair memory immune responses, which can lead to uncontrolled CMV reactivation and clinical viremia. CMV reactivation is known to drive a process termed memory inflation, in which the CMV reactive CD8 T cell population expands and adopts an aged highly differentiated phenotype. Recent studies have found that memory inflation is accelerated in recipients of solid organ transplantation. However, it is unknown whether this effect is due to immunosuppression, the end-stage organ disease preceding transplant, or some other factor. To address this question, we have analyzed T cell differentiation and memory inflation in rheumatoid arthritis (RA) patients both before and one year after initiation of immunosuppressive therapy. Preliminary data indicate that T cells in RA patients have a highly differentiated state pre-treatment that is maintained a year after initiation of immunosuppressive therapy. This includes a CD8 T cell population with evidence of immune aging. Differentiation states and aging were similar in CMV seropositive and seronegative RA patients. Overall these findings indicate that independent of CMV serostatus, RA is associated with highly differentiated and aged T cells. In contrast to this stability of differentiation state, there is evidence of memory inflation of CMV-responsive T cells in the CMV seropositive RA patients, suggesting that immunosuppression may induce memory inflation in this setting as well as transplantation. Further study is needed to determine how immunosuppression induces memory inflation.