Cutting Edge: Regulation of CD8+ T Cell Effector Population Size

Kemp, Roslyn A.; Powell, T J; Dwyer, David; Dutton, Richard

doi:10.4049/jimmunol.173.5.2923

Cited by 39 publications

(51 citation statements)

References 24 publications

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“…However, other experimental models using peptide-loaded DCs to stimulate CD8 ϩ T cells have reported little competition for access to APCs (45). The differences could relate to the amount of Ag used to stimulate naive precursors because dendritic cells can be loaded with high peptide levels that may not be similar to the levels generated during infection with live immunogens in vivo.…”

Section: Discussionmentioning

confidence: 92%

Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

Faassen

Saldanha

Gilbertson

et al. 2005

The Journal of Immunology

105

101

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During infection with lymphocytic choriomeningitis virus, CD8+ T cells differentiate rapidly into effectors (CD62LlowCD44high) that differentiate further into the central memory phenotype (CD62LhighCD44high) gradually. To evaluate whether this CD8+ T cell differentiation program operates in all infection models, we evaluated CD8+ T cell differentiation during infection of mice with recombinant intracellular bacteria, Listeria monocytogenes (LM) and Mycobacterium bovis (BCG), expressing OVA. We report that CD8+ T cells primed during infection with the attenuated pathogen BCG-OVA differentiated primarily into the central subset that correlated to reduced attrition of the primed cells subsequently. CD8+ T cells induced by LM-OVA also differentiated into central phenotype cells first, but the cells rapidly converted into effectors in contrast to BCG-OVA. Memory CD8+ T cells induced by both LM-OVA as well as BCG-OVA were functional in that they produced cytokines and proliferated extensively in response to antigenic stimulation after adoptive transfer. During LM-OVA infection, if CD8+ T cells were guided to compete for access to APCs, then they received reduced stimulation that was associated with increased differentiation into the central subset and reduced attrition subsequently. Similar effect was observed when CD8+ T cells encountered APCs selectively during the waning phase of LM-OVA infection. Taken together, our results indicate that the potency of the pathogen can influence the differentiation and fate of CD8+ T cells enormously, and the extent of attrition of primed CD8+ T cells correlates inversely to the early differentiation of CD8+ T cells primarily into the central CD8+ T cell subset.

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Section: Discussionmentioning

confidence: 92%

Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

Faassen

Saldanha

Gilbertson

et al. 2005

The Journal of Immunology

105

101

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“…It is possible that the extent of this infection results in a large enough pool of antigen-presenting DCs or other APCs to overwhelm the competition for these cells, but competition for a particular peptide͞MHC complex presented by these cells is retained. Another report used a system similar to ours and observed only competition between clones of the same specificity (13). However, when testing competition between clones of different specificities mice were immunized with target peptides pulsed onto separate DC populations and not the same DCs.…”

Section: Discussionmentioning

confidence: 99%

“…A key factor in studies of T cell competition is the ratio of T cells to DCs, as increasing the availability of DCs and antigen will eventually eliminate the effect of competition (6,13). Our model uses transfer of a larger than physiological number of antigenspecific CD8 T cells to allow detailed measurements of the extent and quality of their response.…”

Section: Discussionmentioning

confidence: 99%

“…The response to these subdominant epitopes was restored either in the absence of the dominant response or if the dominant and subdominant epitopes were presented on separate antigen-presenting cells (APCs). Competition between T cells of different specificities has not been observed in all systems tested, however, and its existence is therefore controversial (4,12,13). This competition appears to occur at the level of the APC, because it does not occur if the antigens are presented by separate APCs.…”

mentioning

confidence: 99%

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CD8 T cell competition for dendritic cellsin vivois an early event in activation

Willis¹,

Kappler

Marrack

2006

Proc. Natl. Acad. Sci. U.S.A.

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“…After activation by Ag, T cells are triggered into a rapid burst of ∼10-15 cell divisions resulting in profound expansion (42). Cell division can occur extremely rapidly, as fast as 2-3 h (43), and independently of further TCR triggering, at least to some extent (44).…”

Section: Discussionmentioning

confidence: 99%

Clonally Diverse T Cell Homeostasis Is Maintained by a Common Program of Cell-Cycle Control

Hogan

Shuvaev

Commenges

et al. 2013

The Journal of Immunology

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Lymphopenia induces T cells to undergo cell divisions as part of a homeostatic response mechanism. The clonal response to lymphopenia is extremely diverse, and it is unknown whether this heterogeneity represents distinct mechanisms of cell-cycle control or whether a common mechanism can account for the diversity. We addressed this question by combining in vivo and mathematical modeling of lymphopenia-induced proliferation (LIP) of two distinct T cell clonotypes. OT-I T cells undergo rapid LIP accompanied by differentiation that superficially resembles Ag-induced proliferation, whereas F5 T cells divide slowly and remain naive. Both F5 and OT-I LIP responses were most accurately described by a single stochastic division model where the rate of cell division was exponentially decreased with increasing cell numbers. The model successfully identified key biological parameters of the response and accurately predicted the homeostatic set point of each clone. Significantly, the model was successful in predicting interclonal competition between OT-I and F5 T cells, consistent with competition for the same resource(s) required for homeostatic proliferation. Our results show that diverse and heterogenous clonal T cell responses can be accounted for by a single common model of homeostasis.

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Cutting Edge: Regulation of CD8+ T Cell Effector Population Size

Cited by 39 publications

References 24 publications

Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

CD8 T cell competition for dendritic cellsin vivois an early event in activation

Clonally Diverse T Cell Homeostasis Is Maintained by a Common Program of Cell-Cycle Control

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