The Repertoires of Circulating Human CD8+ Central and Effector Memory T Cell Subsets Are Largely Distinct (original) (raw)

Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes

The Journal of Immunology, 2007

In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected the functional properties of ex vivo effector-memory (EM) CD45RA ؊ CCR7 ؊ T lymphocytes present within the circulating CD8 ؉ T cell pool of healthy individuals. Our studies show that EM T cells are heterogeneous and are subdivided based on differential CD27 and CD28 expression into four subsets. EM 1 (CD27 ؉ CD28 ؉ ) and EM 4 (CD27 ؊ CD28 ؉ ) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7R␣. EM 1 cells also have a relatively short replicative history and display strong ex vivo telomerase activity. Therefore, these cells are closely related to central-memory (CD45RA ؊ CCR7 ؉ ) cells. In contrast, EM 2 (CD27 ؉ CD28 ؊ ) and EM 3 (CD27 ؊ CD28 ؊ ) cells express mediators characteristic of effector cells, whereby EM 3 cells display stronger ex vivo cytolytic activity and have experienced larger numbers of cell divisions, thus resembling differentiated effector (CD45RA ؉ CCR7 ؊ ) cells. These data indicate that progressive up-regulation of cytolytic activity and stepwise loss of CCR7, CD28, and CD27 both characterize CD8 ؉ T cell differentiation. Finally, memory CD8 ؉ T cells not only include centralmemory cells but also EM 1 cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively.

Expression of CD8? identifies a distinct subset of effector memory CD4 + T lymphocytes

Immunology, 2006

Circulating CD4 + CD8 + T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4 + CD8 + T cells in rhesus macaques. Two distinct populations of CD4 + CD8 + T cells were identified: the dominant one was CD4 hi CD8 lo and expressed the CD8aa homodimer, while the minor population was CD4 lo CD8 hi and expressed the CD8ab heterodimer. The majority of CD4 hi CD8a lo T cells exhibited an activated effector/memory phenotype (CCR5 lo CD7-CD28-HLA-DR +) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4 hi CD8a lo T cells compared to single-positive CD4 + T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4 hi CD8a lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4 hi CD8a lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4 + T cells expressing CD8a represent an effector/memory subset of CD4 + T cells and that this cell population can be depleted during the course of SIV infection.

Fully Functional Memory CD8 T Cells in the Absence of CD4 T Cells

The Journal of Immunology, 2004

173:969-975; ; J Immunol References http://www.jimmunol.org/content/173/2/969.full#ref-list-1 , 24 of which you can access for free at: cites 41 articles This article Subscriptions http://jimmunol.org/subscriptions is online at: The Journal of Immunology Information about subscribing to

Expression of CD8? identifies a distinct subset of effector memory CD4⁺T lymphocytes

Immunology, 2006

Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs

PLOS Pathogens, 2016

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8 + T cells in human lymphoid organs. This revealed two distinct populations of memory CD8 + T cells, that were CD69 + CD103 + and CD69 + CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8 + memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8 + T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8 + T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

A committed tissue-resident memory T cell precursor within the circulating CD8+ effector T cell pool

Journal of Experimental Medicine

An increasing body of evidence emphasizes the role of tissue-resident memory T cells (TRM) in the defense against recurring pathogens and malignant neoplasms. However, little is known with regard to the origin of these cells and their kinship to other CD8+ T cell compartments. To address this issue, we followed the antigen-specific progeny of individual naive CD8+ T cells to the T effector (TEFF), T circulating memory (TCIRCM), and TRM pools by lineage-tracing and single-cell transcriptome analysis. We demonstrate that a subset of T cell clones possesses a heightened capacity to form TRM, and that enriched expression of TRM–fate-associated genes is already apparent in the circulating TEFF offspring of such clones. In addition, we demonstrate that the capacity to generate TRM is permanently imprinted at the clonal level, before skin entry. Collectively, these data provide compelling evidence for early stage TRM fate decisions and the existence of committed TRM precursor cells in the ...

The generation and differentiation of memory CD8 T cell responses in health and disease

Memory CD8 T cells offer increased protection to immune hosts by rapidly eliminating pathogen-infected cells during re-infection. Generating and sustaining a protective memory CD8 T cell response is considered a hallmark of adaptive immunity. Extensive research has been devoted to understanding the parameters affecting memory CD8 T cell generation after infection or immunization in order to design the most effective vaccines. An accepted notion in the field is that increased protection from reinfection is afforded by the generation of a large number of memory CD8 T cells. Consecutive prime-boost immunization strategies that elicit secondary responses are often used to increase the absolute numbers of memory CD8 T cells.

in the Absence of CD4 T Cells Fully Functional Memory CD8 T Cells

2000

Maintenance of the human memory T cell repertoire by subset and tissue site

Genome Medicine, 2021

BackgroundImmune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity.MethodsWe analyzed the TCR repertoire of the major memory CD4+and CD8+T cell subsets (TEM, TCM, TEMRA, and TRM) isolated from blood and/or lymphoid organs (spleen, lymph nodes, bone marrow) and lungs of nine organ donors, and blood of three living individuals spanning five decades of life. High-throughput sequencing of the variable (V) portion of individual TCR genes for each subset, tissue, and individual were analyzed for clonal diversity, expansion and overlap between lineage,...

The Repertoires of Circulating Human CD8+ Central and Effector Memory T Cell Subsets Are Largely Distinct (original) (raw)

Related papers