Low-Affinity Ligands for the TCR Drive Proliferation of Mature CD8+ T Cells in Lymphopenic Hosts

Goldrath, Ananda W.; Bevan, Michael J.

doi:10.1016/s1074-7613(00)80093-x

Cited by 503 publications

(485 citation statements)

References 39 publications

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“…3A). The discrepancy between our and other studies is probably related to the analysis of a polyclonal T cell response in our study rather than the mono-specific response of transgenic T cells used by other investigators [7][8][9][10][11]. As expected, F10 tumor vaccination increased the CD44 hi CD62L lo population in both normal mice and RLM.…”

Section: Vaccinated Rlm Have a High Percentage Of Memory/effector T Ccontrasting

confidence: 86%

“…However, there are significant differences between antigen-and homeostasis-driven memory T cell differentiation in terms of kinetics, rate of cell division, and pattern of CD69, CD25, CD44 and CD62L expression. A distinction between memory-like T cells in RLM and antigen-driven memory/effector T cells is that memory-like T cells reportedly do not significantly down-regulate CD62L expression, or up-regulate CD25 and CD69 expression [7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that during homeostasisdriven proliferation, naive T cells acquire a memory-like or activated phenotype characterized by increased expression of the surface markers CD44 and Ly6-c, but not down-regulated CD62L expression, which differs from "true" antigen-experienced memory/effector T cells [7][8][9][10][11]. Consistently, we found that it was the irradiation and reconstitution manipulation rather than vaccination that increased the percentage of CD44 hi CD62L hi cells (from 34.8% to 50.8% in unvaccinated mice and from 34.8% to 44.7% in vaccinated mice) and CD8 + Ly6-c + cells (data not shown).…”

Section: Vaccinated Rlm Have a High Percentage Of Memory/effector T Cmentioning

confidence: 99%

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Anti‐tumor T cell response and protective immunity in mice that received sublethal irradiation and immune reconstitution

Urba

Liu

et al. 2003

Eur J Immunol

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To test whether homeostasis-driven T cell proliferation in reconstituted lymphodepleted hosts would improve the therapeutic efficacy of tumor vaccines, normal mice and reconstituted lymphopenic mice (RLM; C57BL/6 mice rendered lymphopenic with sublethal totalbody irradiation and reconstituted with naive splenocytes) were used in the vaccination and challenge experiments with weakly immunogenic F10 melanoma cells. Only limited protection was observed in vaccinated normal mice (16.7%), whereas significantly greater protection was induced in vaccinated RLM (63.2%). Protective immunity in RLM depended on CD8 T cells. Following vaccination, a significant increase in the percentage of CD44 hi CD62L lo T cells was detected in the tumor vaccine-draining lymph node (TVDLN) of vaccinated RLM compared to that of vaccinated normal mice. After in vitro stimulation, effector T cells generated from TVDLN of vaccinated RLM produced more IFN-+ than T cells from vaccinated normal mice, and contained more melanoma-specific T cells, as assessed by ELISA and intracellular cytokine staining. This study suggests that vaccination of reconstituted lymphopenic hosts could elicit superior anti-tumor immunity compared to normal hosts, highlighting the potential clinical benefit of performing tumor vaccination during immune reconstitution.

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Section: Vaccinated Rlm Have a High Percentage Of Memory/effector T Ccontrasting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Vaccinated Rlm Have a High Percentage Of Memory/effector T Cmentioning

confidence: 99%

See 1 more Smart Citation

Anti‐tumor T cell response and protective immunity in mice that received sublethal irradiation and immune reconstitution

Urba

Liu

et al. 2003

Eur J Immunol

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“…Different growth factors may be involved in homeostatic proliferation of CD4 and CD8 T cells; however, if anything, these growth factors appear to be favoring CD8 cells (Jameson, 2002;Marrack et al, 2000;Sprent and Surh, 2003). Moreover, the survival of naïve CD8 T cells depends on the recognition of major histocompatibility complex MHC class I molecules, which are more abundantly expressed in the periphery of MHC class II molecules recognized by CD4 T cells (Ernst et al, 1999;Goldrath and Bevan, 1999b;Jameson, 2002). Interestingly, this difference between CD4 and CD8 T-cell homeostasis is not limited to the naïve T-cell compartment; memory T cells show similarly divergent behavior.…”

Section: Differential Homeostatic Controls In Cd4 and Cd8 T Cellsmentioning

confidence: 99%

Aging and T-cell diversity☆

Goronzy

Lee

Weyand

2007

Experimental Gerontology

237

187

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Naïve and memory CD4 and CD8 T cells represent a highly dynamic system with constant homeostatic and antigen-driven proliferation, influx, and loss of T cells. Thymic activity dwindles with age and essentially ceases in the later decades of life, severely constraining the generation of new T cells. Homeostatic control mechanisms are very effective to maintain a large and diverse subset of naïve CD4 T cells for many years up to the 8 th decade of life, but eventually and abruptly fail at about the age of 75 years. In contrast, the CD8 T cell compartment is more unstable, with progressive diminution of naïve T cells and increasing loss of diversity already during mid adulthood. Vaccination strategies need to aim at developing a broad repertoire of memory T cells before the critical time period when the naïve CD4 T-cell repertoire collapses. Research efforts need to aim at understanding the homeostatic control mechanisms to ultimately expand the time period of repertoire stability.Adaptive immune responses are initiated when T cells recognize endogenous antigen on activated and mature antigen-presenting cells. Successful responses depend on the repertoire of existing T cells (Nikolich-Zugich et al., 2004). The diversity of the T-cell compartment determines whether T cells are available that recognize antigen with high avidity. The frequency of each T-cell specificity in the existing repertoire influences how fast an initial immune recognition event can be amplified to generate a sufficient number of effector cells. Consequently, the naïve T-cell repertoire is highly diverse, providing the ability to recognize the universe of exogenous and potentially dangerous antigens. In contrast, the memory T-cell repertoire is selected by previous antigen exposure. Each memory T cell clone is present in larger frequency, guaranteeing a more rapid response upon re-exposure to the same antigen. Homeostatic regulation is important not only to control the size of the T-cell compartment, but also the composition of naïve and memory T cells, as well as the diversity of each T-cell compartment (Goldrath and Bevan, 1999a). T cell homeostasis and ageThe homeostatic control mechanisms have to deal with exogenous and endogenous challenges (Freitas and Rocha, 2000;Jameson, 2002). The T-cell compartment is a highly dynamic T-cell reservoir with sometimes conflicting kinetics of singular components that compete for space. The most evident example is the clonal expansion that occurs after naïve or memory T cells encounter antigen. This clonal expansion is dramatic and has been estimated to include 10 to 15 population doublings followed by equally rapid clonal contraction with a majority of *Corresponding author. Mailing address: Lowance Center for Human Immunology, Emory University School of Medicine, 101 Woodruff Circle #1003, Atlanta, GA 30322. Phone: (404) 727-7310. Fax: (404) 727-7371. E-mail: E-mail: jgoronz@emory.edu.. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As...

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“…The MHC molecules delivering survival signals to naïve T cells are believed to be the same type of MHC/self-peptide molecules delivering positive selection signals in the thymus. Whether the peptides are identical to the peptides presented in the thymus during positive selection is still under debate [171][172][173]. However, it is generally agreed that Bcl-2 protein family may be one of the major effector molecules downstream of TCR/MHC and IL-7 signaling to control naïve T cell survival [163,164].…”

Section: Maintenance Of Naïve T Cellsmentioning

confidence: 99%

The role of apoptosis in the development and function of T lymphocytes

et al. 2005

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Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dysregulation of apoptosis in the immune system results in autoimmunity, tumorogenesis and immunodeficiency. Two major pathways lead to apoptosis: the intrinsic cell death pathway controlled by Bcl-2 family members and the extrinsic cell death pathway controlled by death receptor signaling. These two pathways work together to regulate T lymphocyte development and function.

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Low-Affinity Ligands for the TCR Drive Proliferation of Mature CD8+ T Cells in Lymphopenic Hosts

Cited by 503 publications

References 39 publications

Anti‐tumor T cell response and protective immunity in mice that received sublethal irradiation and immune reconstitution

Anti‐tumor T cell response and protective immunity in mice that received sublethal irradiation and immune reconstitution

Aging and T-cell diversity☆

The role of apoptosis in the development and function of T lymphocytes

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