ALBERT

Description: by Eleonora Li Causi, Suraj C. Parikh, Lindsey Chudley, David M. Layfield, Christian H. Ottensmeier, Freda K. Stevenson, Gianfranco Di Genova CD4 + T helper memory (Th mem ) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Th mem cells as expected, but was accompanied by parallel increase of Th mem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Th mem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Th mem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Th mem cells were activated (CD38 High HLA-DR + ), cycling or recently divided (Ki-67 + ), and apparently vulnerable to death (IL-7Rα Low and Bcl-2 Low ). In contrast, bystander Th mem cells were resting (CD38 Low HLA-DR - Ki-67 - ) with high expression of IL-7Rα and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Th mem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines.