Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells

BK Cho, VP Rao, Q Ge, HN Eisen, J Chen - The Journal of …, 2000 - rupress.org
BK Cho, VP Rao, Q Ge, HN Eisen, J Chen
The Journal of experimental medicine, 2000rupress.org
The developmental requirements for immunological memory, a central feature of adaptive
immune responses, is largely obscure. We show that as naive CD8 T cells undergo
homeostasis-driven proliferation in lymphopenic mice in the absence of overt antigenic
stimulation, they progressively acquire phenotypic and functional characteristics of antigen-
induced memory CD8 T cells. Thus, the homeostasis-induced memory CD8 T cells express
typical memory cell markers, lyse target cells directly in vitro and in vivo, respond to lower …
The developmental requirements for immunological memory, a central feature of adaptive immune responses, is largely obscure. We show that as naive CD8 T cells undergo homeostasis-driven proliferation in lymphopenic mice in the absence of overt antigenic stimulation, they progressively acquire phenotypic and functional characteristics of antigen-induced memory CD8 T cells. Thus, the homeostasis-induced memory CD8 T cells express typical memory cell markers, lyse target cells directly in vitro and in vivo, respond to lower doses of antigen than naive cells, and secrete interferon γ faster upon restimulation. Like antigen-induced memory T cell differentiation, the homeostasis-driven process requires T cell proliferation and, initially, the presence of appropriate restricting major histocompatibility complexes, but it differs by occurring without effector cell formation and without requiring interleukin 2 or costimulation via CD28. These findings define repetitive cell division plus T cell receptor ligation as the basic requirements for naive to memory T cell differentiation.
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