Logo image
Manipulating the rate of memory CD8+ T cell generation after acute infection
Journal article   Peer reviewed

Manipulating the rate of memory CD8+ T cell generation after acute infection

Vladimir P Badovinac and John T Harty
The Journal of immunology (1950), Vol.179(1), pp.53-63
07/01/2007
DOI: 10.4049/jimmunol.179.1.53
PMID: 17579021

View Online

Abstract

Infection with Listeria monocytogenes elicits expansion in numbers of Ag-specific CD8+ T cells, which then undergo programmed contraction. The remaining cells undergo further phenotypic and functional changes with time, eventually attaining the qualities of memory CD8+ T cells. In this study, we show that L. monocytogenes-specific CD8+ T cell populations primed in antibiotic-pretreated mice undergo brief effector phase, but rapidly develop phenotypic (CD127(high), CD43(low)) and functional (granzyme B(low), IL-2-producing) characteristics of memory CD8+ T cells. These early memory CD8+ T cells were capable of substantial secondary expansion in response to booster challenge at day 7 postinfection, resulting in significantly elevated numbers of secondary effector and memory CD8+ T cells and enhanced protective immunity compared with control-infected mice. Although early expansion in numbers is similar after L. monocytogenes infection of antibiotic-pretreated and control mice, the absence of sustained proliferation coupled with decreased killer cell lectin-like receptor G-1 up-regulation on responding CD8+ T cells may explain the rapid effector to memory CD8+ T cell transition. In addition, antibiotic treatment 2 days post-L. monocytogenes challenge accelerated the generation of CD8+ T cells with memory phenotype and function, and this accelerated memory generation was reversed in the presence of CpG-induced inflammation. Together, these data show that the rate at which Ag-specific CD8+ T cell populations acquire memory characteristics after infection is not fixed, but rather can be manipulated by limiting inflammation that will in turn modulate the timing and extent to which CD8+ T cells proliferate and up-regulate killer cell lectin-like receptor G-1 expression.
Acute Disease CD8-Positive T-Lymphocytes - pathology Dendritic Cells - immunology Mice, Inbred C57BL Immunophenotyping Mice, Transgenic Adoptive Transfer Ampicillin - administration & dosage Immunologic Memory - drug effects Listeriosis - prevention & control Cell Differentiation - immunology Lymphocyte Activation - immunology Animals Immunization, Secondary Cell Differentiation - drug effects Lymphocyte Activation - drug effects Listeriosis - immunology Listeriosis - pathology CD8-Positive T-Lymphocytes - metabolism Mice Mice, Inbred BALB C CD8-Positive T-Lymphocytes - immunology Dendritic Cells - transplantation

Details

Metrics

Logo image