Memory T cells have gene expression patterns intermediate between naïve and effector

Holmes, Susan; He, Michael; Xu, Tong; Lee, Peter P.

doi:10.1073/pnas.0501437102

Cited by 59 publications

(52 citation statements)

References 20 publications

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“…This represents a reduction of 2 to 3 log in required material, compared with previous studies using microarrays on primary lymphocytes (13)(14)(15)(16)33). It opens new possibilities of using microarray analysis, for instance to study gene expression profiles in rare cell subsets and/or in case of limited access to samples (e.g., small blood samples, biopsies).…”

Section: Discussionmentioning

confidence: 90%

“…To obtain the amount of materials (i.e., mRNA) necessary to perform the experiments, previous studies of primary human lymphocytes by microarray analysis used at least 10 5 cell samples (13)(14)(15)(16). In an effort to reduce the required amount of sample, we have worked on a method that could enable us to apply microarray technology to the analysis of low cell numbers.…”

Section: Validation Of the Methodology Using Immortalized Cellsmentioning

confidence: 99%

“…ϩ and CCR7 Ϫ (or CD27 Ϫ ) phenotype (i.e., overlapping with stage 5 CD8 ϩ T cell subset to a large extent) (13,14).…”

Section: Klrd1 Ifit1 Fgr Tnfr1 and Itgb2 In Cd8mentioning

confidence: 99%

“…3, a and b), FACS sorted from a single blood sample of 20 ml. Because previous studies showed a good uniformity of microarray data on lymphocyte subsets between different donors (13,14), experiments were performed only on two donor blood samples (still representing a total of 20 microarrays). For both CD4 ϩ or CD8 ϩ lineages, the probes obtained for each subset were hybridized in a competitive manner against the probes from respective naive cell pool standards (composed of three independent FACS isolated and amplified 1000 CD4 ϩ or CD8 ϩ cell samples).…”

Section: T Cell Differentiationmentioning

confidence: 99%

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Sensitive Gene Expression Profiling of Human T Cell Subsets Reveals Parallel Post-Thymic Differentiation for CD4+ and CD8+ Lineages

Appay

Bosio

Lokan

et al. 2007

The Journal of Immunology

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The differentiation of CD4+ or CD8+ T cells following priming of naive cells is central in the establishment of the immune response against pathogens or tumors. However, our understanding of this complex process and the significance of the multiple subsets of differentiation remains controversial. Gene expression profiling has opened new directions of investigation in immunobiology. Nonetheless, the need for substantial amount of biological material often limits its application range. In this study, we have developed procedures to perform microarray analysis on amplified cDNA from low numbers of cells, including primary T lymphocytes, and applied this technology to the study of CD4 and CD8 lineage differentiation. Gene expression profiling was performed on samples of 1000 cells from 10 different subpopulations, defining the major stages of post-thymic CD4+ or CD8+ T cell differentiation. Surprisingly, our data revealed that while CD4+ and CD8+ T cell gene expression programs diverge at early stages of differentiation, they become increasingly similar as cells reach a late differentiation stage. This suggests that functional heterogeneity between Ag experienced CD4+ and CD8+ T cells is more likely to be located early during post-thymic differentiation, and that late stages of differentiation may represent a common end in the development of T-lymphocytes.

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Section: Discussionmentioning

confidence: 90%

Section: Validation Of the Methodology Using Immortalized Cellsmentioning

confidence: 99%

“…ϩ and CCR7 Ϫ (or CD27 Ϫ ) phenotype (i.e., overlapping with stage 5 CD8 ϩ T cell subset to a large extent) (13,14).…”

Section: Klrd1 Ifit1 Fgr Tnfr1 and Itgb2 In Cd8mentioning

confidence: 99%

Section: T Cell Differentiationmentioning

confidence: 99%

See 2 more Smart Citations

Sensitive Gene Expression Profiling of Human T Cell Subsets Reveals Parallel Post-Thymic Differentiation for CD4+ and CD8+ Lineages

Appay

Bosio

Lokan

et al. 2007

The Journal of Immunology

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“…ϩ T cells that generate memory cells (78,79). In addition to this marker, we have also ϩ T cells does not change from primary infection to viral persistence as measured by their IFN-␥ production capacity.…”

Section: Discussionmentioning

confidence: 96%

Memory Generation and Maintenance of CD8+ T Cell Function during Viral Persistence

Cush¹,

Anderson²,

Ravneberg³

et al. 2007

The Journal of Immunology

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During infection with viruses that establish latency, the immune system needs to maintain lifelong control of the infectious agent in the presence of persistent Ag. By using a γ-herpesvirus (γHV) infection model, we demonstrate that a small number of virus-specific central-memory CD8+ T cells develop early during infection, and that virus-specific CD8+ T cells maintain functional and protective capacities during chronic infection despite low-level Ag persistence. During the primary immune response, we show generation of CD8+ memory T cell precursors expressing lymphoid homing molecules (CCR7, L-selectin) and homeostatic cytokine receptors (IL-7α, IL-2/IL-15β). During long-term persistent infection, central-memory cells constitute 20–50% of the virus-specific CD8+ T cell population and maintain the expression of L-selectin, CCR7, and IL-7R molecules. Functional analyses demonstrate that during viral persistence: 1) CD8+ T cells maintain TCR affinity for peptide/MHC complexes, 2) the functional avidity of CD8+ T cells measured as the capacity to produce IFN-γ is preserved intact, and 3) virus-specific CD8+ T cells have in vivo killing capacity. Next, we demonstrate that at 8 mo post-virus inoculation, long-term CD8+ T cells are capable of mediating a protective recall response against the establishment of γHV68 splenic latency. These observations provide evidence that functional CD8+ memory T cells can be generated and maintained during low-load γHV68 persistence.

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Development of CTL memory despite arrested clonal expansion

Stipdonk¹,

Sluijter²,

Han³

et al. 2008

Eur J Immunol

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Activation of a cytotoxic T lymphocyte (CTL) response in an antigen-exposed lymph node involves a great diversity of encounters between naive CTL and APC that differ in both duration and quality. This broad spectrum of priming events instigates a complex blend of CTL developmental pathways. Using an experimental system that allows tight control over CTL priming, we have singled out defined priming events and analyzed the impact of the resulting instructional program on the effector and memory phases of the CTL response. As expected, prolonged antigenic stimulation induces potent CTL expansion, effector function and CTL memory. In contrast, CTL that have received suboptimal stimulation fail to undergo extensive expansion. Nevertheless these arrested CTL persist long term and acquire memory function. Thus, our data demonstrate that CTL memory can develop as a result of a suboptimal stimulation that causes arrested clonal expansion. Key words: CD8 T cells Á Cell differentiation Á Cellular proliferation Á Memory cells IntroductionT cells protect the health of an organism by mounting a wellorchestrated immune response consisting of proliferation, effector cell differentiation, contraction and memory formation. These aspects of the T cell response are programmed during the initial contact of naive T cells with antigen-presenting cells (APC) [1][2][3][4]. The strength of the signal that is delivered during primary stimulation determines the quality of the T cell differentiation program [5,6]. The interrelationship between the T cell types that represent the different stages of the immune response, the naive T cells, effector T cells and memory T cells, is still a matter of debate. Some studies support a linear differentiation model wherein naive T cells first develop into effector cells and thereafter into memory cells [7][8][9]. Other studies suggest (partially) parallel pathways of effector and memory T cell generation [10, 11].As a consequence of the primary T cell response, different subsets of memory T cells can emerge, in particular the central memory (Tcm) and effector memory (Tem) T cells. Although the exact phenotypic definitions of the two subsets differ slightly between mouse and human T cells and among different research groups, it is generally accepted that Tcm cells express CD62L and therefore preferentially localize in lymphoid tissues, whereas Tem cells lack these features and therefore mainly reside in the blood and non-lymphoid tissues (reviewed in [12,13]). The two memory subsets also complement each other functionally, in that Tem cells exhibit immediate effector function while Tcm cells cause expansion of responding cells through extensive cell division. The lineage relationship between the subsets of memory cells is still unclear, calling for further study on the factors deciding between the formation of Tcm versus Tem cells [14][15][16][17]. A recent study has shed some light on this issue by showing that high T cell precursor frequencies favor Tcm cell formation while low precursor frequencies p...

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Memory T cells have gene expression patterns intermediate between naïve and effector

Abstract: The biological basis underlying differentiation of naïve (NAI) T cells into effector (EFFE) and memory (MEM) cells is incompletely un

Cited by 59 publications

References 20 publications

Sensitive Gene Expression Profiling of Human T Cell Subsets Reveals Parallel Post-Thymic Differentiation for CD4+ and CD8+ Lineages

Sensitive Gene Expression Profiling of Human T Cell Subsets Reveals Parallel Post-Thymic Differentiation for CD4+ and CD8+ Lineages

Memory Generation and Maintenance of CD8+ T Cell Function during Viral Persistence

Development of CTL memory despite arrested clonal expansion

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