T-cell quality in memory and protection: implications for vaccine design

Abstract

T cells mediate effector functions through a variety of mechanisms. Recently, multiparameter flow cytometry has allowed a simultaneous assessment of the phenotype and multiple effector functions of single T cells; the delineation of T cells into distinct functional populations defines the quality of the response. New evidence suggests that the quality of T-cell responses is crucial for determining the disease outcome to various infections. This Review highlights the importance of using multiparameter flow cytometry to better understand the functional capacity of effector and memory T-cell responses, thereby enabling the development of preventative and therapeutic vaccine strategies for infections.

Human peripheral blood and bone marrow Epstein–Barr virus‐specific T‐cell repertoire in latent infection reveals distinct memory T‐cell subsets

“…In accordance with the proposed differentiation model of Seder the CD8 1 triple cytokine producers in our study had an intermediate differentiation memory phenotype based on the CCR7 expression level (Fig. 4C) [48].In previous studies we could detect enhanced frequencies of tumor-reactive and CMV-specific central memory T cells in BM [44,45,57]. Palendira et al…”

“…Highest levels of CCR7 expression were found on the TNF 1 IL-2 1 and TNF-single producing cells for both CD4 1 and CD8 1 T cells, corresponding to an early-differentiated central memory phenotype. In contrast, CD8 1 IFN-g 1 TNF 1 cells and CD4 1 IFN-g-producing cells (single or in combination) had lowest CCR7 expression, corresponding to a late-differentiated effector memory phenotype [48]. In the CD8 1 T-cell compartment, triple cytokine as well as IFN-g single-producing cells had a significantly higher CCR7 expression than IFN-g 1 TNF 1 producers.…”

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+ T cells

“…These individual T cells produce between two and five different effector functions, which is important as multiple effector functions are deployed by the most effective T cell responses, as demonstrated in infection and cancer 35. Polyfunctional T cells have also been shown to be imperative for a vaccination to provide persistent immunity against a pathogen 36. This study shows that all T cell subpopulations develop a proportion of cells with a polyfunctional phenotype as a consequence of IMCgp100 treatment.…”

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

“…The Th1 cells that secrete IL‐2 or TNF‐α or both can develop into IFN‐γ producers, and these cells can provide a supply of memory CD4 + T cells with effector potential 50 . As very few memory T cells will be sustained from a single IFN‐γ producer, a vaccine that induces mainly this response will probably not elicit protective immunity 51 . Interestingly, intranasal immunisation with the pandemic H5N1 virosomal vaccine adjuvanted with matrix M induced much lower frequencies of TNF‐α + /IL‐2 + CD4 + T cells in the mouse spleen 30 compared with the current study.…”

“…To our knowledge, this study is the first to show that an intranasal pandemic influenza vaccine formulated with a mucosal adjuvant induces high frequencies of multifunctional CD4 + T cells in mice. Multifunctional T cells have been associated with better clinical outcomes of patients infected with human immunodeficiency virus (HIV), 51 reduced HIV replication 52 and protection elicited against smallpox by priming with vaccinia virus 53 . However, the strongest evidence to date for the importance of multifunctional CD4 + T cells in eliciting a protective immune response is in the mouse model of Leishmania major infection 48 , 54 .…”