Terminal differentiation of T cells during CMV & HIV infection


Cytomegalovirus (PHIL CDC, ID#14429)

Cytomegalovirus (CMV) is a chronic viral infection and part of the herpesvirus group, and is associated with a decreased CD4/CD8 ratio and increased systemic inflammation. Most notably, CMV infection is also associated with increased expansion of terminally differentiated T cells. HIV-CMV co-infection is quite high among HIV-infected individuals, where CMV infection may drive the ‘immune senescent’ phenotype.

Researchers from the Netherlands and UK participated as part of the Co-morBidity in Relation to AIDS (COBRA) collaboration to evaluate activation and terminal differentiation of T cells in HIV patients on ART. The COBRA cohort was used to assess treated HIV infection. Peripheral blood mononuclear cell (PBMC) samples were used to determine the expression of T cell differentiation through naïve, central memory, effector memory, transitional memory, and terminally differentiated effector memory. In contrast, T cell activation was evaluated through the proportion of CD38 and HLA-DR within CD4 or CD8 T cell populations. Additionally, CMV reactivation, recurrent CMV antigen exposure, and antibody maturation was determined.

Results indicated that HIV-positive participants were more likely to be infected with CMV than their HIV-negative counterparts. Despite being on ART, HIV-positive participants had incomplete CD4+ T-cell restoration and increased CD8 T cell counts. T cell activation was higher in HIV-positive (with ART) participants. Furthermore, HIV-positive individuals had lowered naïve CD4+ and effector memory CD8+ cells, but no differences associated with the other types of cells analyzed. However, when comparing HIV-positive participants to blood bank donor cells, there was a higher percentage of effector memory CD4+ and CD8+ cells. Through linear regression analysis, it was determined that both CMV infection and HIV infection were independently associated with T cell activation, exhaustion, and terminal differentiation. HIV infection was associated with increased T cell exhaustion, while CMV infection was associated with decreased CD8+ T cell exhaustion. Lastly, HIV-positive participants had increased total and high avidity CMV antibody titers.

The authors of this study demonstrated that HIV-positive participants individuals face several differences in immune-associated cells. However, CMV infection may explain higher levels of terminally differentiated T cells in both HIV-positive and HIV-negative populations. The multiple regression analysis uncovered the underlying variable of CMV infection, which may be responsible for influencing T cell terminal differentiation during HIV infection. This wide-ranging study provides insight of the impact of infectious disease on T cell developmental biology.

Journal Article: Booiman et al., 2017. Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls. PLOS One.



Article by Rebecca Ng

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation