Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo
- 21 September 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 109 (3), 1086-1094
- https://doi.org/10.1182/blood-2006-03-011643
Abstract
Functional studies show that programming of CD8+ T cells occurs early after initial antigen encounter within as little as 2 hours. To define the molecular basis of these events, we transferred TCR transgenic T cells from F5 Rag−/− mice into naive recipients and stimulated them with recombinant vaccinia expressing the immunodominant influenza epitope NP366-374. Transcription in epitope-specific cytotoxic T lymphocytes (CTLs) was analyzed using Affymetrix 430 2.0 GeneChips and quantitative polymerase chain reaction (PCR). We demonstrated an early transcriptional burst with the greatest number of genes reaching peak expression 12 hours after stimulation. Using in vivo cytotoxicity assays we demonstrated that early up-regulation of cytolytic genes was accompanied by acquisition of killing capacity within 24 hours of stimulation. However, T-cell proliferation was not observed until 48 hours. We therefore conclude that clonal expansion rather than acquisition of effector function is the rate-limiting step in the development of a primary CTL response.Keywords
This publication has 31 references indexed in Scilit:
- p18INK4c and p27KIP1 are required for cell cycle arrest of differentiated myotubesExperimental Cell Research, 2004
- T-cell priming by dendritic cells in lymph nodes occurs in three distinct phasesNature, 2004
- Gene expression profiling reveals a highly specialized genetic program of plasma cellsBlood, 2003
- Exploration, normalization, and summaries of high density oligonucleotide array probe level dataBiostatistics, 2003
- Lineage relationship and protective immunity of memory CD8 T cell subsetsNature Immunology, 2003
- Cyclin G2 Associates with Protein Phosphatase 2A Catalytic and Regulatory B′ Subunits in Active Complexes and Induces Nuclear Aberrations and a G1/S Phase Cell Cycle ArrestJournal of Biological Chemistry, 2002
- Effector and memory T-cell differentiation: implications for vaccine developmentNature Reviews Immunology, 2002
- Lymphocyte-Mediated CytotoxicityAnnual Review of Immunology, 2002
- Fas and Perforin Pathways as Major Mechanisms of T Cell-Mediated CytotoxicityScience, 1994
- Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient miceNature, 1994