Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation models have been proposed, suggesting CD4 memory T cell development from naive precursors either with or without an effector-stage intermediate, respectively. Here, we address this question by using newly available techniques for the identification and isolation of effector T cells secreting effector cytokines. In adoptive cell transfers into normal, nonlymphopenic mice, we show that long-lived virus-specific memory T cells can efficiently be generated from purified interferon gamma-secreting T helper (Th) type 1 and interleukin (IL)-4- or IL-10-secreting Th2 effectors primed in vitro or in vivo. Importantly, such effector-derived memory T cells were functional in viral challenge infections. They proliferated vigorously, rapidly modulated IL-7 receptor expression, exhibited partial stability and flexibility of their cytokine patterns, and exerted differential effects on virus-induced immunopathology. Thus, cytokine-secreting effectors can evade activation-induced cell death and develop into long-lived functional memory cells. These findings demonstrate the efficiency of linear memory T cell differentiation and encourage the design of vaccines and immune cell therapies based on differentiated effector T cells.

Original publication

DOI

10.1084/jem.20071855

Type

Journal article

Journal

J Exp Med

Publication Date

21/01/2008

Volume

205

Pages

53 - 61

Keywords

Animals, Cell Differentiation, Cytokines, Flow Cytometry, Immunologic Memory, Interferon-gamma, Interleukin-10, Interleukin-4, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, T-Lymphocytes, Th1 Cells, Th2 Cells