Differential Kinetics of Antigen-Specific CD4+ and CD8+ T Cell Responses in the Regression of Retrovirus-Induced Sarcomas

Schepers, Koen; Toebes, Mireille; Sotthewes, Gitte; Vyth‐Dreese, Florry A.; Dellemijn, Trees A. M.; Melief, Cornelis J.M.; Ossendorp, Ferry; Schumacher, Ton N.

doi:10.4049/jimmunol.169.6.3191

Cited by 78 publications

(88 citation statements)

References 55 publications

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“…Although the frequencies of Agspecific CD4 ϩ cells do not reach those that have been observed for Ag-specific CD8 ϩ cells (34,35), CD4 ϩ T cell expansion is nevertheless likely to be critical for Th cell function. To test whether CD4 ϩ cells can also be activated and expand upon in vivo recognition of an MHC class I ligand, we adoptively transferred OT-Ior F5-modified CD4 ϩ cells into recipient mice and challenged the mice with a recombinant influenza A strain (inflova) that expresses the OVA 257-264 epitope.…”

Section: Ag-specific Cd4mentioning

confidence: 96%

Generation of T Cell Help through a MHC Class I-Restricted TCR

Kessels

Schepers

Boom

et al. 2006

The Journal of Immunology

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CD4+ T cells that are activated by a MHC class II/peptide encounter can induce maturation of APCs and promote cytotoxic CD8+ T cell responses. Unfortunately, the number of well-defined tumor-specific CD4+ T cell epitopes that can be exploited for adoptive immunotherapy is limited. To determine whether Th cell responses can be generated by redirecting CD4+ T cells to MHC class I ligands, we have introduced MHC class I-restricted TCRs into postthymic murine CD4+ T cells and examined CD4+ T cell activation and helper function in vitro and in vivo. These experiments indicate that Ag-specific CD4+ T cell help can be induced by the engagement of MHC class I-restricted TCRs in peripheral CD4+ T cells but that it is highly dependent on the coreceptor function of the CD8β-chain. The ability to generate Th cell immunity by infusion of MHC class I-restricted Th cells may prove useful for the induction of tumor-specific T cell immunity in cases where MHC class II-associated epitopes are lacking.

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Section: Ag-specific Cd4mentioning

confidence: 96%

Generation of T Cell Help through a MHC Class I-Restricted TCR

Kessels

Schepers

Boom

et al. 2006

The Journal of Immunology

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“…1A, B). To assure virus specificity of CD8 + T cells, the effector T cells were stained with an MHC class I tetramer specific for the subpopulation of cells recognizing the H-2D b -restricted Friend murine leukemia helper virus (F-MuLV) glycosylated gag epitope (H-2D b / gagL) [13]. Interestingly, only very low levels of tetramer-positive CD8 + T cells were detected during the first 10 days of infection (Fig.…”

Section: Effector Cd8 + T Cells Were Induced During the First 2 Weeksmentioning

confidence: 99%

“…The D b -GagL tetramers were constructed by Koen Schepers and Ton Schumacher (The Netherlands Cancer Institute, Amsterdam) using a peptide in which all three cysteine residues were replaced with amino-butyric acid to prevent inter-peptide disulfide bonding [13]. This variant peptide is recognized by polyclonal D b -GagL-specific CD8 + T cells as determined by intracellular IFN-c staining.…”

Section: Tetramers and Tetramer Stainingmentioning

confidence: 99%

Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

Zelinskyy¹,

Kraft²,

Schimmer³

et al. 2006

Eur J Immunol

120

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Cytolytic CD8 + T cells are critical for the control of acute Friend virus (FV) infection yet they fail to completely eliminate the virus during chronic infection because they are functionally impaired by regulatory T cells (Treg). We performed a kinetic analysis of T cell responses during FV infection to determine when dysfunction of CD8 + T cells and suppressive activity of CD4 + regulatory T cells develops. At 1 week post infection, virusspecific CD8 + T cells with effector phenotype and cytolytic potential expanded. Peak expansion was found at 12 days post infection, correlating with peak viral loads. After 2 weeks when viral loads dropped, numbers of activated CD8 + T cells started to decline. However, a population of virus-specific CD8 + T cells with effector phenotype was still detectable subsequently, but these cells had lost their ability to produce granzymes and to degranulate cytotoxic molecules. Contemporaneous with the development of CD8 + T cell dysfunction, different CD4 + T cell populations expressing cell surface markers for Treg and the Treg-associated transcription factor Foxp3 expanded. Transfer as well as depletion experiments indicated that regulatory CD4 + cells developed during the second week of FV infection and subsequently suppressed CD8 + T cell functions, which was associated with impaired virus clearance.

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“…For detection of D b -GagL-specific CD8 + T cells, nucleated lymph nodes and spleen cells were stained with APC-labeled anti-CD8 (Ly-2) (eBioscience), FITC-labeled CD43 (1B11) (Becton Dickinson), and phycoerythrin-labeled MHC class I H2-D b tetramers specific for FV GagL peptide (Beckman Coulter) (16,17).…”

Section: Methodsmentioning

confidence: 99%

Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8 ⁺ T cells and reduces chronic retroviral set points

Dietze

Zelinskyy

Gibbert

et al. 2011

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

121

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Although chronic infections with viruses such as HIV and hepatitis C virus have been associated with regulatory T cell (Treg)-mediated suppression of virus-specific CD8 + T-cell activity, no causal relationship between Tregs and chronic viral set points has been established. Using transgenic mice in which Tregs can be selectively ablated, we now show that transient depletion of Tregs during a chronic retroviral infection allows exhausted CD8 + T cells to regain antiviral functions, including secretion of cytokines, production of cytotoxic molecules, and virus-specific cytolytic activity. Furthermore, short-term Treg ablation resulted in long-term reductions in chronic virus loads. These results demonstrate that Tregmediated immunosuppression can be a significant factor in the maintenance of chronic viral infections and that Treg-targeted immunotherapy could be a valuable component in therapeutic strategies to treat chronic infectious diseases.cytotoxic T cells | retrovirus | friend virus

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Differential Kinetics of Antigen-Specific CD4+ and CD8+ T Cell Responses in the Regression of Retrovirus-Induced Sarcomas

Cited by 78 publications

References 55 publications

Generation of T Cell Help through a MHC Class I-Restricted TCR

Generation of T Cell Help through a MHC Class I-Restricted TCR

Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8 ⁺ T cells and reduces chronic retroviral set points

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Differential Kinetics of Antigen-Specific CD4+ and CD8+ T Cell Responses in the Regression of Retrovirus-Induced Sarcomas

Cited by 78 publications

References 55 publications

Generation of T Cell Help through a MHC Class I-Restricted TCR

Generation of T Cell Help through a MHC Class I-Restricted TCR

Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infection

Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8 + T cells and reduces chronic retroviral set points

Contact Info

Product

Resources

About

Kinetics of CD8⁺ effector T cell responses and induced CD4⁺ regulatory T cell responses during Friend retrovirus infection

Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8 ⁺ T cells and reduces chronic retroviral set points