The nature of the lymphopenic environment dictates protective function of homeostatic-memory CD8 + T cells
- 25 November 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (47), 18484-18489
- https://doi.org/10.1073/pnas.0806487105
Abstract
A functional memory T cell pool is critical for resistance to pathogen reinfection. Lymphopenia produces memory-like CD8(+) T cells through homeostatic proliferation, and such "HP-memory" cells can control lethal bacterial infections similarly to conventional, antigen-experienced, memory T cells. These 2 pathways for memory T cell generation are quite distinct. We show here, however, that similar factors are required for production of protective memory CD8 T cells via both homeostatic and conventional pathways. Induction of protective HP-memory CD8 T cells requires CD4(+) T cell "help," which we show is antigen nonspecific yet requires CD40L-CD40 interactions with host cells. The functional competence of HP-memory CD8 T cells also requires release of endogenous bacterial components (which follows irradiation-induced lymphopenia), potentially mimicking the role of adjuvants in conventional immune responses. Lymphopenic environments lacking these key factors support similar CD8 T cell homeostatic proliferation and the acquisition of memory phenotype, yet the HP-memory cells generated are defective in pathogen elimination. These findings suggest unexpected parallels in the requirements for generating protective memory CD8 T cells by distinct pathways, and they suggest ways to bolster immune competence during recovery from lymphopenia.Keywords
This publication has 28 references indexed in Scilit:
- Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signalingJCI Insight, 2007
- Effector and Memory CTL DifferentiationAnnual Review of Immunology, 2007
- Naive CD4 T cells constitutively express CD40L and augment autoreactive B cell survivalProceedings of the National Academy of Sciences of the United States of America, 2006
- Signals required for programming effector and memory development by CD8+ T cellsImmunological Reviews, 2006
- The clone size of peripheral CD8 T cells is regulated by TCR promiscuityThe Journal of Experimental Medicine, 2006
- The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cellsNature Immunology, 2006
- Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell–dendritic cell interactionNature, 2006
- Helping the CD8+ T-cell responseNature Reviews Immunology, 2004
- Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor LymphocytesScience, 2002
- Defective TCR expression in transgenic mice constructed using cDNA‐based α‐ and β‐chain genes under the control of heterologous regulatory elementsImmunology & Cell Biology, 1998