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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.

Type

Journal article

Journal

The Journal of experimental medicine

Publication Date

14/01/2008

Volume

205

Pages

53 - 61

Addresses

Institute of Experimental Immunology, University Hospital Zurich, CH-8091 Zurich, Switzerland. Loehning@drfz.de

Keywords

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