Apoptosis and loss of virus-specific CD8+ T-cell memory

Welsh, Raymond M.; Bahl, Kapil; Wang, Xiaoting Z.

doi:10.1016/j.coi.2004.03.020

Cited by 24 publications

(22 citation statements)

References 42 publications

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“…Therefore, it is unlikely that infection with CMV would impair EBV-specific T cell responses. Our findings do not corroborate the data retrieved from mice studies where competition between memory T cells was shown (11)(12)(13)(14), especially because CMV will give rise to latent infection and these mice studies showed that the attrition of memory T cells was most prominent upon infection with a persistent virus (15). We conclude from our data that the size of the human memory T cell pool is not so strictly regulated that the entrance of new cells leads to the disappearance of others.…”

Section: Discussioncontrasting

confidence: 55%

“…Several studies in mice have shown that infection with a new virus, and consequent emergence of an additional population of memory cells, results in permanent loss of pre-existing memory T cells against unrelated pathogens (11)(12)(13). In this way, the overall size of the memory T cell pool remains relatively constant, and memory T cells have to compete for physical space and/or homeostatic cytokines (14). There appears to be a difference between T cells specific for viruses that are cleared by the host and viruses that persist.…”

Section: Differential Usage Of Cellular Niches By Cytomegalovirus Vermentioning

confidence: 99%

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Differential Usage of Cellular Niches by Cytomegalovirus versus EBV- and Influenza Virus-Specific CD8+ T Cells

Leeuwen¹,

Koning²,

Remmerswaal³

et al. 2006

The Journal of Immunology

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Immunological memory provides long-term protection against reinfection or reactivation of pathogens. Murine memory T cell populations may be compressed following infections with new pathogens. Humans have to retain memory T cells directed against a variety of microbes for many decades. Under these circumstances, the effect of pathogens that mount robust T cell reactivity on the pre-existing memory directed against unrelated microbes is unknown. In this study, we studied peripheral blood memory CD8+ T cells directed against different viruses following primary CMV infection in renal transplant recipients. The entrance of CMV-specific CD8+ T cells expanded the Ag-primed CD8+ T cell compartment rather than competing for space with pre-existing memory T cells specific for persistent or cleared viruses. Neither numbers nor phenotype of EBV- or influenza-specific CD8+ T cells was altered by primary CMV infection. CMV-specific CD8+ T cells accumulated over time, resulting in increased total CD8+ T cell numbers. Additionally, they acquired a highly differentiated cytolytic phenotype that was clearly distinct from EBV- or influenza-reactive T cells. Thus, the human immune system appears to be flexible and is able to expand when encountering CMV. In view of the phenotypic differences between virus-specific T cells, this expansion may take place in cellular niches different from those occupied by EBV- or influenza-specific T cells, thereby preserving immunity to these pathogens.

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Section: Discussioncontrasting

confidence: 55%

Section: Differential Usage Of Cellular Niches By Cytomegalovirus Vermentioning

confidence: 99%

Differential Usage of Cellular Niches by Cytomegalovirus versus EBV- and Influenza Virus-Specific CD8+ T Cells

Leeuwen¹,

Koning²,

Remmerswaal³

et al. 2006

The Journal of Immunology

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“…61,63,64 Many viral infections in mouse and human induce a substantial loss in lymphocyte and leukocyte numbers in the early stages of infections. 65 A substantial loss in CD8 and CD4 T cell number during the first 5 days of LCMV infection parallels the levels of type 1 IFN production, does not occur in type 1 IFN receptor ko mice, 66 is blocked by antibody to type 1 IFN 67 and is mimicked by IFN-inducing toll receptor agonists, such as poly I:C. 66 The apoptotic loss of memory occurs prior to cell division. 63,66,68 An in silico virtual immune system model, IMMSIM, which unlike a biological system can selectively turn off either active or passive attrition, predicted that without the active attrition and apoptosis of memory T cells early in infection, crossreactive T cells might overwhelmingly dominate the response to an infection.…”

Section: Heterologous Immunity and T Cell Crossreactivitymentioning

confidence: 99%

Vaccination and heterologous immunity: educating the immune system

Gil¹,

Kenney²,

Mishra³

et al. 2015

Transactions of the Royal Society of Tropical Medicine and Hygiene

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This review discusses three inter-related topics: (1) the immaturity of the neonatal and infant immune response; (2) heterologous immunity, where prior infection history with unrelated pathogens alters disease outcome resulting in either enhanced protective immunity or increased immunopathology to new infections, and (3) epidemiological human vaccine studies that demonstrate vaccines can have beneficial or detrimental effects on subsequent unrelated infections. The results from the epidemiological and heterologous immunity studies suggest that the immune system has tremendous plasticity and that each new infection or vaccine that an individual is exposed to during a lifetime will potentially alter the dynamics of their immune system. It also suggests that each new infection or vaccine that an infant receives is not only perturbing the immune system but is educating the immune system and laying down the foundation for all subsequent responses. This leads to the question, is there an optimum way to educate the immune system? Should this be taken into consideration in our vaccination protocols?

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“…One intriguing possibility is that SL9 provokes a cross-reactive memory T cell response to one or more common pathogen(s). This would also explain why SL9 reactivity is rare in acute infection, when cross-reactive memory cells are driven into apoptosis (heterologous immunity) (64). From the perspective of vaccine design, it implies that it may be difficult to induce useful SL9 responses with the native Gag protein in HLA-A2 ϩ people.…”

Section: Discussionmentioning

confidence: 99%

Degeneracy and Repertoire of the Human HIV-1 Gag p1777–85 CTL Response

Kan‐Mitchell

Bajcz

Schaubert

et al. 2006

The Journal of Immunology

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CD8+ CTL responses are important for the control of HIV-1 infection. The immunodominant HLA-A2-restricted Gag epitope, SLYNTVATL (SL9), is considered to be a poor immunogen because reactivity to it is rare in acute infection despite its paradoxical dominance in patients with chronic infection. We have previously reported SL9 to be a help-independent epitope in that it primes highly activated CTLs ex vivo from CD8+ T cells of seronegative healthy donors. These CTLs produce sufficient cytokines for extended autocrine proliferation but are sensitive to activation-induced cell death, which may cause them to be eliminated by a proinflammatory cytokine storm. Here we identified an agonist variant of the SL9 peptide, p41 (SLYNTVAAL), by screening a large synthetic combinatorial nonapeptide library with ex vivo-primed SL9-specific T cells. p41 invariably immunized SL9-cross-reactive CTLs from other donors ex vivo and H-2Db β2m double knockout mice expressing a chimeric HLA-A*0201/H2-Db MHC class I molecule. Parallel human T cell cultures showed p41-specific CTLs to be less fastidious than SL9-CTLs in the level of costimulation required from APCs and the need for exogenous IL-2 to proliferate (help dependent). TCR sequencing revealed that the same clonotype can develop into either help-independent or help-dependent CTLs depending on the peptide used to activate the precursor CD8+ T cells. Although Ag-experienced SL9-T cells from two patients were also sensitive to IL-2-mediated cell death upon restimulation in vitro, the loss of SL9 T cells was minimized with p41. This study suggests that agonist sequences can replace aberrantly immunogenic native epitopes for the rational design of vaccines targeting HIV-1.

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Apoptosis and loss of virus-specific CD8+ T-cell memory

Cited by 24 publications

References 42 publications

Differential Usage of Cellular Niches by Cytomegalovirus versus EBV- and Influenza Virus-Specific CD8+ T Cells

Differential Usage of Cellular Niches by Cytomegalovirus versus EBV- and Influenza Virus-Specific CD8+ T Cells

Vaccination and heterologous immunity: educating the immune system

Degeneracy and Repertoire of the Human HIV-1 Gag p1777–85 CTL Response

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