UNIGE document Scientific Article
previous document  unige:19137  next document
add to browser collection
Title

Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors

Authors
Lohning, Max
Hegazy, Ahmed N.
Busse, Dorothea
Lang, Karl S.
Hofer, Thomas
Radbruch, Andreas
Zinkernagel, Rolf M.
show hidden authors show all authors [1 - 9]
Published in Journal of Experimental Medicine. 2008, vol. 205, no. 1, p. 53-61
Abstract 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.
Keywords AnimalsCell DifferentiationCytokines/metabolismFlow Cytometry*Immunologic MemoryInterferon-gamma/metabolismInterleukin-10/metabolismInterleukin-4/metabolismLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicModels, BiologicalT-Lymphocytes/*physiology/virologyTh1 Cells/*physiology/virologyTh2 Cells/*physiology/virology
Identifiers
PMID: 18195073
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://jem.rupress.org/content/205/1/53.full.pdf
Structures
Research group Infections virales persistantes et maladies autoimmunes (849)
Citation
(ISO format)
LOHNING, Max et al. Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. In: Journal of Experimental Medicine, 2008, vol. 205, n° 1, p. 53-61. https://archive-ouverte.unige.ch/unige:19137

174 hits

0 download

Update

Deposited on : 2012-03-27

Export document
Format :
Citation style :