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Transient enhanced IL-2R signaling early during priming rapidly amplifies development of functional CD8+ T effector-memory cells.


ABSTRACT: Much is known concerning the cellular and molecular basis for CD8(+) T memory immune responses. Nevertheless, conditions that selectively support memory generation have remained elusive. In this study, we show that an immunization regimen that delivers TCR signals through a defined antigenic peptide, inflammatory signals through LPS, and growth and differentiation signals through the IL-2R initially favors Ag-specific CD8(+) T cells to develop rapidly and substantially into T effector-memory cells by TCR transgenic OVA-specific OT-I CD8(+) T cells. Amplified CD8(+) T memory development depends upon a critical frequency of Ag-specific T cells and direct responsiveness to IL-2. A homologous prime-boost immunization protocol with transiently enhanced IL-2R signaling in normal mice led to persistent polyclonal Ag-specific CD8(+) T cells that supported protective immunity to Listeria monocytogenes. These results identify a general approach for amplified T memory development that may be useful to optimize vaccines aimed at generating robust cell-mediated immunity.

SUBMITTER: Castro I 

PROVIDER: S-EPMC3478487 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Transient enhanced IL-2R signaling early during priming rapidly amplifies development of functional CD8+ T effector-memory cells.

Castro Iris I   Dee Michael J MJ   Malek Thomas R TR  

Journal of immunology (Baltimore, Md. : 1950) 20120926 9


Much is known concerning the cellular and molecular basis for CD8(+) T memory immune responses. Nevertheless, conditions that selectively support memory generation have remained elusive. In this study, we show that an immunization regimen that delivers TCR signals through a defined antigenic peptide, inflammatory signals through LPS, and growth and differentiation signals through the IL-2R initially favors Ag-specific CD8(+) T cells to develop rapidly and substantially into T effector-memory cel  ...[more]

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