Homeostatic expansion and phenotypic conversion of naïve T cells in response to self peptide/MHC ligands

AUTOR(ES)

Kieper, William C.

FONTE

The National Academy of Sciences

RESUMO

Recent data suggest that survival of resting, naïve T cells requires an interaction with self MHC molecules. From analysis of the class I MHC-restricted T cell receptor transgenic strain OT-I, we report a different response. Rather than merely surviving, these T cells proliferated slowly after transfer into T-depleted syngeneic hosts. This expansion required both T cell “space” and expression of normal levels of self class I MHC molecules. Furthermore, we demonstrate that during homeostatic expansion in a suitable environment, naïve phenotype (CD44low) OT-I T cells converted to memory phenotype (CD44med/high), despite the absence of foreign antigenic stimulation. On the other hand, cells undergoing homeostatic expansion did not acquire cytolytic effector function. The significance of these data for reactivity of T cells with self peptide/MHC ligands and the implications for normal and abnormal T cell homeostasis are discussed.

Documentos Relacionados

• Prevalent CD8+ T cell response against one peptide/MHC complex in autoimmune diabetes
• Naive T cells proliferate strongly in neonatal mice in response to self-peptide/self-MHC complexes
• In vitro evolution of a T cell receptor with high affinity for peptide/MHC
• Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells
• Positive selection of self-MHC-reactive T cells by individual peptide–MHC class II complexes