Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation

Stipdonk, Marianne J.B. van; Lemmens, Edward E.; Schoenberger, Stephen P.

doi:10.1038/87730

Cited by 788 publications

(681 citation statements)

References 45 publications

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“…Interestingly, late clearance did not hinder the activation of the donor T cells [76]. This corroborates with several reports that demonstrate antigenic stimulation, before APC clearance, is all that is required to initiate activation and proliferation of T cells [80,81].…”

Section: Effects Of Lymphodepleting Radiation and Chemotherapy On Apcsupporting

confidence: 90%

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Klebanoff

Khong

Antony

et al. 2005

Trends in Immunology

411

288

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Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine 'sinks' for homeostatic γ C -cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4 + CD25 + regulatory T (Treg) cells that suppress tumorreactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigenpresenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer.

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Section: Effects Of Lymphodepleting Radiation and Chemotherapy On Apcsupporting

confidence: 90%

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Klebanoff

Khong

Antony

et al. 2005

Trends in Immunology

411

288

View full text Add to dashboard Cite

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“…Earlier studies reported similar synchrony within the CD8 + T cell compartment, among CTL specific for different epitopes from the same pathogen [2,21]. Further analysis of this synchrony within T cell responses revealed that the in vivo kinetics of expansion and contraction are determined very early during the initial phase of the immune response and are remarkably independent of later environmental factors and changes, such as the in vivo halflife of a particular antigen or the duration of infection [2,22,[24][25][26]. The results of our comparative study indicate that the initial activation and 'programming' of epitopespecific CD4 + and CD8 + T cells occur within a similar time frame during infection.…”

Section: Discussionmentioning

confidence: 74%

Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations

et al. 2003

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Our knowledge about the kinetics and dynamics of complex pathogen-specific CD8 + T cell responses and the in vivo development of CD8 + memory T cells has increased substantially over the past years; in comparison, relatively little is known about the CD4 + T cell compartment. We monitored and directly compared the phenotypical changes of pathogen (Listeria monocytogenes)-specific CD8 + and CD4 + T cell responses under conditions leading to effective and long-lasting protective immunity. We found that the general kinetics of bacteriaspecific CD8 + and CD4 + T cells during the effector and post-effector phases are synchronized. However, later during the memory phase, CD8 + and CD4 + T cell populations differ substantially. Whereas CD8 + memory T cell populations with immediate effector function are readily detectable in lymphoid and non-lymphoid tissues and remain remarkably stable in size, antigen-specific CD4 + effector-memory T cells decline continuously in frequency over time. These findings have important implications for the better understanding of the in vivo development of protective immunity towards intracellular pathogens.

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“…Whether this difference was due to in vivo versus in vitro stimulation or the nature of the stimulus was not clear. Within the first 20 h of stimulation, T cells receive the signals they need to undergo a pre-programmed expansion phase that appears to be independent of further T cell activation [33][34][35][36][37]. Recent evidence also suggests that CD8 T cells kill antigen-presenting DC during the first few days of the response [38].…”

Section: Introductionmentioning

confidence: 99%

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

Dawicki

Watts

2004

Eur J Immunol

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4-1BBL -/-mice have a defect in recall CD8 + T cell responses to viruses, whereas CD4 + T cell responses to virus are unimpaired in these mice. In contrast, both CD4 + and CD8 + T cells respond to 4-1BB ligand (4-1BBL) in vitro. To clarify the role of 4-1BB/4-1BBL in CD4 + versus CD8 + T cell responses in vivo, we compared CD4 (OT-II) and CD8 (OT-I) TCR transgenic T cells responding to the same antigen in an in vivo adoptive transfer model in 4-1BBL +/+ versus 4-1BBL -/-mice. During primary and secondary responses, expression of 4-1BB on in vivo-activated TCR transgenic T cells was earlier and more transient than previously observed in vitro, correlating with expression of the early activation antigen CD69 and preceding the transition to the CD44 hi state. Although 4-1BB is expressed early in the primary response, there was no effect of 4-1BBL deficiency on initial CD8 T cell expansion and only a minor effect on initial CD4 T cell expansion. The major effect of 4-1BB/4-1BBL interaction is on the T cell recall response. This is due to effects of 4-1BBL on maintenance of T cell numbers at the end of the primary response with additional effects of 4-1BBL on secondary expansion of T cells.

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Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation

Cited by 788 publications

References 45 publications

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

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Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation

Cited by 788 publications

References 45 publications

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Differences in maintenance of CD8+ and CD4+ bacteria‐specific effector‐memory T cell populations

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

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Product

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Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations