We studied here the long-term maintenance of distinct populations of T helper type 1 (THI)-lineage cells in vivo and found that effector THI cells, defined by their secretion of interferon-gamma (IFN-gamma), are short-lived and do not efficiently develop into long-term memory THI cells. In contrast, a population of activated THI-lineage cells that did not secrete IFN-gamma after primary antigenic stimulation persisted for several months in vivo and developed the capacity to secrete IFN-gamma upon subsequent stimulation. These data suggest that a linear differentiation pathway, as defined by the transition from IFN-gamma-producing to resting memory cells, is relatively limited in vivo and support a revised model for THI memory differentiation.
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