In Vivo Expansion of the Residual Tumor Antigen-Specific CD8<sup>+</sup>T Lymphocytes That Survive Negative Selection in Simian Virus 40 T-Antigen-Transgenic Mice

Schell, Todd D.

doi:10.1128/jvi.78.4.1751-1762.2004

Cited by 11 publications

(18 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, few studies have focused on T cells that are specifically reactive toward subdominant or immunorecessive tumor epitopes expressed by spontaneous tumors. Previously, our laboratory found that Tag epitope V-specific T CD8 could be expanded from the endogenous T cell repertoire in line 501 SV40 Tag-transgenic mice (18) and line SV11 mice (17). However, the effect on tumor growth was not addressed.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it was necessary to immunize specifically against epitope V to detect T cells that recognize this immunorecessive epitope. The residual response to epitope V in SV11 mice is composed primarily of lower avidity T CD8 which recognize Tag epitope V peptide 1,000-to 10,000-fold less efficiently than B6-derived T cells (17). Importantly, booster immunizations expand a population of Tag V-specific clones that effectively lyse wt Tag transformed cells and have avidities similar to T cells derived from B6 mice.…”

mentioning

confidence: 95%

“…Previous work demonstrated that the residual epitope V specific T CD8 in SV11 mice are optimally expanded following a prime and boost regimen (17). Given that primary immunization promoted TCR-V cell expansion in the spleen and promoted migration to the brain (Fig.…”

Section: A Prime-boost Approach Promotes Tcr-v Cell Accumulation In Tmentioning

confidence: 99%

“…To study the behavior of naive Tag-V-specific T CD8 in response to Tag-expressing tumors, epitope V-specific T CD8 from TCR-transgenic mice were transferred into SV11 mice with advanced tumors. Line TCR-V-transgenic mice express the TCR ␣-and ␤-chains derived from the epitope V-specific clone Y-5 (9) on the C57BL/6 background and have been previously characterized (17,27). The epitope V-specific Y-5 clone was generated in a C57BL/6 mouse immunized with a Tag variant cell line expressing only the immunorecessive epitope V (9).…”

Section: Naive Tcr-transgenic T Cd8 (Tcr-v) Recognize Endogenous Epitmentioning

confidence: 99%

“…The characteristics which contribute toward the immunorecessive nature of epitope V might also permit survival of epitope V-specific T CD8 in mice that develop Tag-induced tumors. This was recently investigated in line SV11 mice, where a subset of T CD8 specific for Tag epitope V are spared and seed the peripheral lymphoid tissues despite Tag expression in the thymus (17). In contrast, T CD8 specific for epitopes I, II/III, and IV are deleted.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Accumulation of CD8+ T Cells in Advanced-Stage Tumors and Delay of Disease Progression following Secondary Immunization against an Immunorecessive Epitope

Ryan

Schell

2006

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Self-reactive T cells that survive the process of positive and negative selection during thymocyte development represent potential effector cells against tumors that express these same self-Ags. We have previously shown that CD8+ T lymphocytes (TCD8) specific for an immunorecessive epitope, designated epitope V, from the SV40 large T Ag (Tag) escape thymic deletion in line SV11 Tag-transgenic mice. In contrast, these mice are tolerant to the three most dominant Tag epitopes. The majority of the residual epitope V-specific TCD8 have a low avidity for the target epitope, but a prime/boost regimen can expand higher avidity clones in vivo. Whether higher avidity TCD8 targeting this epitope are affected by Tag-expressing tumors in the periphery or can be recruited for control of tumor progression remains unknown. In the current study, we determined the fate of naive TCR-transgenic TCD8 specific for Tag epitope V (TCR-V cells) following transfer into SV11 mice bearing advanced-stage choroid plexus tumors. The results indicate that TCR-V cells are rapidly triggered by the endogenous Tag and acquire effector function, but fail to accumulate within the tumors. Primary immunization enhanced TCR-V cell frequency in the periphery and promoted entry into the brain, but a subsequent booster immunization caused a dramatic accumulation of TCR-V T cells within the tumors and inhibited tumor progression. These results indicate that epitope V provides a target for CD8+ T cells against spontaneous tumors in vivo, and suggests that epitopes with similar properties can be harnessed for tumor immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

Section: A Prime-boost Approach Promotes Tcr-v Cell Accumulation In Tmentioning

confidence: 99%

Section: Naive Tcr-transgenic T Cd8 (Tcr-v) Recognize Endogenous Epitmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Accumulation of CD8+ T Cells in Advanced-Stage Tumors and Delay of Disease Progression following Secondary Immunization against an Immunorecessive Epitope

Ryan

Schell

2006

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

CD8⁺ T‐cell cross‐competition is governed by peptide–MHC class I stability

et al. 2011

View full text Add to dashboard Cite

A major contributing factor to the final magnitude and breadth of CD8+ T-cell responses to complex antigens is immunodomination, where CD8+ T cells recognizing their cognate ligand inhibit the proliferation of other CD8+ T cells engaged with the same APC. In this study, we examined how the half-life of cell surface peptide–MHC class I complexes influences this phenomenon. We found that primary CD8+ T-cell responses to DNA vaccines in mice are shaped by competition among responding CD8+ T cells for nonspecific stimuli early after activation and prior to cell division. The susceptibility of CD8+ T cells to ‘domination’ was a direct correlate of higher kinetic stability of the competing CD8+ T-cell cognate ligand. When high affinity competitive CD8+ T cells were deleted by self-antigen expression, competition was abrogated. These findings show, for the first time to our knowledge, the existence of regulatory mechanisms that direct the responding CD8+ T-cell repertoire toward epitopes with high-stability interactions with MHC class I molecules. They also provide an insight into factors that facilitate CD8+ T-cell coexistence, with important implications for vaccine design and delivery.

show abstract

Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors

Yorty

Tevethia

Schell

2007

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

We previously established a model to study CD8(+) T cell (T(CD8))-based adoptive immunotherapy of cancer using line SV11 mice that develop choroid plexus tumors in the brain due to transgenic expression of Simian Virus 40 large T antigen (Tag). These mice are tolerant to the three dominant T(CD8)-recognized Tag epitopes I, II/III and IV. However, adoptive transfer of spleen cells from naïve C57BL/6 (B6) mice prolongs SV11 survival following T(CD8) priming against the endogenous Tag epitope IV. In addition, survival of SV11 mice is dramatically increased following transfer of lymphocytes from Tag-immune B6 mice. In the current study, we compared the kinetics and magnitude of Tag-specific T(CD8) accumulation at the tumor site following adoptive transfer with a high dose of either Tag-immune or naïve donor cells or decreasing doses of Tag-immune lymphocytes. Following adoptive transfer of Tag-immune cells, epitope I- and IV-specific T(CD8) accumulated to high levels in the brain of SV11 mice, peaking at 5-7 days, while epitope IV-specific T(CD8 )derived from naïve donors required three weeks to achieve peak levels. A similar delay in the peak of epitope IV-specific T(CD8) accumulation was observed when tenfold fewer Tag-immune donor cells were administered, reducing control of tumor progression. These results suggest that efficient and prolonged control of established autochthonous tumors is associated with high-level early accumulation of adoptively transferred T cells. We also provide evidence that although multiple specificities are represented in the Tag immune donor lymphocytes, epitope IV-specific donor T(CD8) play a predominant role in control of tumor growth.

show abstract

In Vivo Expansion of the Residual Tumor Antigen-Specific CD8⁺T Lymphocytes That Survive Negative Selection in Simian Virus 40 T-Antigen-Transgenic Mice

Abstract: Mice that express the viral oncoprotein simian virus 40 (SV40) large T antigen (T-Ag؉ T cells with high avidity for epitope V survive negative selection in SV11 mice but can be expanded by specific boosting approaches in the tumor bearing host.

Cited by 11 publications

References 78 publications

Accumulation of CD8+ T Cells in Advanced-Stage Tumors and Delay of Disease Progression following Secondary Immunization against an Immunorecessive Epitope

Accumulation of CD8+ T Cells in Advanced-Stage Tumors and Delay of Disease Progression following Secondary Immunization against an Immunorecessive Epitope

CD8⁺ T‐cell cross‐competition is governed by peptide–MHC class I stability

Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors

Contact Info

Product

Resources

About

In Vivo Expansion of the Residual Tumor Antigen-Specific CD8+T Lymphocytes That Survive Negative Selection in Simian Virus 40 T-Antigen-Transgenic Mice

Abstract: Mice that express the viral oncoprotein simian virus 40 (SV40) large T antigen (T-Ag؉ T cells with high avidity for epitope V survive negative selection in SV11 mice but can be expanded by specific boosting approaches in the tumor bearing host.

Cited by 11 publications

References 78 publications

Accumulation of CD8+ T Cells in Advanced-Stage Tumors and Delay of Disease Progression following Secondary Immunization against an Immunorecessive Epitope

Accumulation of CD8+ T Cells in Advanced-Stage Tumors and Delay of Disease Progression following Secondary Immunization against an Immunorecessive Epitope

CD8+ T‐cell cross‐competition is governed by peptide–MHC class I stability

Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors

Contact Info

Product

Resources

About

In Vivo Expansion of the Residual Tumor Antigen-Specific CD8⁺T Lymphocytes That Survive Negative Selection in Simian Virus 40 T-Antigen-Transgenic Mice

CD8⁺ T‐cell cross‐competition is governed by peptide–MHC class I stability