Phenotypic and Functional Profiling of CD4 T Cell Compartment in Distinct Populations of Healthy Adults with Different Antigenic Exposure

Abstract

BackgroundMultiparameter flow cytometry has revealed extensive phenotypic and functional heterogeneity of CD4 T cell responses in mice and humans, emphasizing the importance of assessing multiple aspects of the immune response in correlation with infection or vaccination outcome. The aim of this study was to establish and validate reliable and feasible flow cytometry assays, which will allow us to characterize CD4 T cell population in humans in field studies more fully.Methodology/Principal FindingsWe developed polychromatic flow cytometry antibody panels for immunophenotyping the major CD4 T cell subsets as well as broadly characterizing the functional profiles of the CD4 T cells in peripheral blood. We then validated these assays by conducting a pilot study comparing CD4 T cell responses in distinct populations of healthy adults living in either rural or urban Kenya. This study revealed that the expression profile of CD4 T cell activation and memory markers differed significantly between African and European donors but was similar amongst African individuals from either rural or urban areas. Adults from rural Kenya had, however, higher frequencies and greater polyfunctionality among cytokine producing CD4 T cells compared to both urban populations, particularly for “Th1” type of response. Finally, endemic exposure to malaria in rural Kenya may have influenced the expansion of few discrete CD4 T cell populations with specific functional signatures.Conclusion/SignificanceThese findings suggest that environmentally driven T cell activation does not drive the dysfunction of CD4 T cells but is rather associated with greater magnitude and quality of CD4 T cell response, indicating that the level or type of microbial exposure and antigenic experience may influence and shape the functionality of CD4 T cell compartment. Our data confirm that it is possible and mandatory to assess multiple functional attributes of CD4 T cell response in the context of infection.

Changes in immunological profile as a function of urbanization and lifestyle

“…The ruralto-urban gradient in these pro-inflammatory profiles supports the finding that populations living in hostile tropical environments display overall greater pro-inflammatory responses than populations living in a temperate environment. 35 Our results are consistent with the finding of Roetynck et al 36 showing that African subjects from a rural community in Kenya displayed a greater overall CD4 + T-cell cytokine response compared with African and European individuals from urban settings. The finding that urban Senegalese display a lower pro-inflammatory profile compared with rural subjects suggests that immunological changes might be associated with a break from traditional lifestyle and lower exposure to infections.…”

Regulatory issues in immunity to liver and blood-stage malaria

“…Likewise, the Th2 subset aids in generating optimal antibody responses against plasmodium infections in humans and mice [32,37,38]. Th17 [39,40], Th22 [41], Tr27 [42], Tregs [43,44 ] and Tfh [45] have all been implicated in control of blood stage malaria. However, the contribution of none of these subsets has been as controversial as that of Tregs in malaria.…”

Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women

“…There are cogent reasons to believe there may be differences in Africans compared to Caucasian cohorts. African cohorts have demonstrated higher baseline levels of T cell activation, significantly different T cell memory differentiation profiles (32, 33), and consistently weaker cellular and humoral reactivity to some vaccines (34, 35). A variety of factors may influence immune activation and therefore normalization of immune profiles after ART, such as genetic, gender and environmental differences, the latter including higher antigenic exposure, diet and gut microbiota.…”