Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help

Sun, Joseph C.; Bevan, Michael J.

doi:10.1126/science.1083317

Cited by 1,088 publications

(973 citation statements)

References 25 publications

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“…(2) Upon antigen encounter, CD4 + recall effector T cells have the potential to rapidly re-expand out of the small memory T cell populations. [34][35][36], providing an explanation for why a loss of CD4 + T cells later during the memory phase does not negatively affect the quality of protective immunity towards Listeria infection, which is mainly mediated by CD8 + memory T cells.…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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

et al. 2003

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“…The precise mechanisms how CD4 T-cells enhance survival and effector function of CD8 T-cells remain unclear. We hypothesize that CD4 T-cells might fulfill in chronic infections a similar function in maintaining memory T-cells as following acute infections 73 . Accordingly, the deterioration in the T-cell response following CD4 depletion in chronic infection might be a consequence of losing these memory-like T-cells.…”

Section: Why Are Memory-like Cells Formed In Chronic Infections?mentioning

confidence: 96%

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

et al. 2014

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Chronic viral infections and malignant tumours induce T cells that have a reduced ability to secrete effector cytokines and have upregulated expression of the inhibitory receptor PD1 (programmed cell death protein 1). These features have so far been considered to mark terminally differentiated 'exhausted' T cells. However, several recent clinical and experimental observations indicate that phenotypically exhausted T cells can still mediate a crucial level of pathogen or tumour control. In this Opinion article, we propose that the exhausted phenotype results from a differentiation process in which T cells stably adjust their effector capacity to the needs of chronic infection. We argue that this phenotype is optimized to cause minimal tissue damage while still mediating a critical level of pathogen control. In contrast to the presently held view of functional exhaustion, this new concept better reflects the pathophysiology and clinical manifestations of persisting infections, and it provides a rationale for emerging therapies that enhance T cell activity in chronic infection and cancer by blocking inhibitory receptors. Daniel T. Utzschneider Division of Immunology and Allergy of the Lausanne University Hospital (CHUV) and Swiss Vaccine Research Institute (SVRI), Lausanne, SwitzerlandDaniel Utzschneider is a PhD student of Dietmar Zehn. His research is focused on T-cell differentiation in chronic infection. Susanne G. Oberle Division of Immunology and Allergy of the Lausanne University Hospital (CHUV) and Swiss Vaccine Research Institute (SVRI), Lausanne, SwitzerlandSusanne Oberle is a PhD student of Dietmar Zehn. Her research interests are focused on investigating T-cell responses in acute and chronic infections. and it provides a rational for emerging therapies that enhance T-cell activity in chronic infection and cancer by blocking inhibitory receptors. Christian Münz PhD

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“…CD4 + T cells are also required for the generation of memory B cell populations. CD4 + T cells are important not only important for the development of humoral responses, but also for the development of functional CD8 + memory T cell populations [13,14]. CD8 + T cell memory is important for immunity against intracellular pathogens, such as viruses, leading to the rapid generation of highly functional effectors that can kill infected cells upon a second encounter with the specific pathogen [15].…”

Section: Effect Of Age On Cd4 + T-cell-and Humoral-mediated Memorymentioning

confidence: 99%

The effect of aging on cognate function and development of immune memory

Haynes

2005

Current Opinion in Immunology

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Immunological memory is one of the central features of the immune system and can be described as the ability of the immune system to respond more efficiently to a second encounter with the same pathogen. The immune system is dramatically affected by age-related changes and it is becoming apparent that immune memory exhibits significant defects as a result of aging. Although immune memory generated during youth functions well into old age, that generated later in life functions poorly. Importantly, age-related defects in the cognate helper function of CD4 + T cells can potentially influence the development of both humoral and cell-mediated immune memory. These defects ultimately result in aged individuals who exhibit reduced responses to both infections and vaccinations.

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Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help

Cited by 1,088 publications

References 25 publications

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

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

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

The effect of aging on cognate function and development of immune memory

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Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help

Cited by 1,088 publications

References 25 publications

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

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

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

The effect of aging on cognate function and development of immune memory

Contact Info

Product

Resources

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

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