Functional management of an antiviral cytotoxic T-cell response

Bachmann, Martin F.; Speiser, Daniel E.; Ohashi, Pamela S.

doi:10.1128/jvi.71.8.5764-5768.1997

Cited by 61 publications

(35 citation statements)

References 39 publications

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“…6A). Effector cells lysed the majority of target cells within 2 h. In contrast, memory T cells required at least 24 h to develop lytic activity, and naive T cells failed to lyse target cells within 24 h. Similar results were obtained using target cells pulsed with the peptide KAVVNIATM, which is selectively recognized by the transgenic TCR [14] (not shown). A similar picture emerged when T cells were stimulated with peptide-pulsed macrophages for various time spans before measurement of lytic activity.…”

Section: Memory T Cells Require Less Than 2 H To Secrete Ifn-q But Resupporting

confidence: 70%

“…It has also been suggested that memory T cells resemble effector cells early after infection and revert to a more quiescent state at later time points [27]. In an alternative model, it was suggested that memory T cells consist of a population of effector-like cells activated by persisting antigen and a population of resting cells similar to naive T cells [3,7,14,28]. The data presented here may help reconciling the different models.…”

Section: What Is a Memory T Cell?mentioning

confidence: 56%

“…Naive T cells are present in very low numbers in unprimed animals and their activation therefore can hardly be studied. Moreover, T cells undergo selection during the establishment of T cell memory and express a heterogeneous set of TCR that are different from the TCR present in the primary response [13,14]. Thus, memory T cells cannot be easily compared with naive T cells at the single-cell level.…”

Section: Introductionmentioning

confidence: 99%

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Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection

Bachmann¹,

Barner²,

Viola³

et al. 1999

Eur. J. Immunol.

172

118

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In the present study, naive T cells were compared with in vivo generated effector and memory T cells expressing the same TCR specific for lymphocytic choriomeningitis virus. Upon restimulation in vitro, the same minimal concentrations of the full agonist peptide p33 and also of weak and partial agonist peptides were required for proliferation of naive, effector and memory T cells, indicating no difference in threshold of activation. However, activation ki-netics were distinct. While effector cytotoxic T cells exhibited immediate ex vivo lytic effector function, naive and memory T cells required 12 h and more exposure to antigen to develop lytic activity. However, both effector and memory T cells contained IFN-+ mRNA in vivo and required less than 3 h for secretion of cytokines upon restimulation in vitro. In contrast, naive T cells did not contain IFN-+ mRNA and required more than 12 h for cytokine secretion. Our results show that memory T cells exhibit a unique phenotype in that they produce cytokines and commit to proliferation as rapidly as effector cells, whereas they resemble naive T cells in the time requirement for development of cytolytic function.

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Section: Memory T Cells Require Less Than 2 H To Secrete Ifn-q But Resupporting

confidence: 70%

Section: What Is a Memory T Cell?mentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection

Bachmann¹,

Barner²,

Viola³

et al. 1999

Eur. J. Immunol.

172

118

View full text Add to dashboard Cite

show abstract

“…The vast majority (>90%) of activated T cells die after the viral infection has been resolved, i.e., under conditions of limiting antigen. It has been proposed that T cells with high affinity TCR would get an antigenic stimulus and survive, whereas the low affinity T cells would be unable to compete for this limiting antigen and would die due to lack of appropriate signaling through the TCR (49, 60). A prediction of this model is that the TCR usage of memory T cells would be different (i.e., narrower) from the antigen-specific T cells activated during the primary response.…”

Section: Discussionmentioning

confidence: 99%

Conserved T Cell Receptor Repertoire in Primary and Memory CD8 T Cell Responses to an Acute Viral Infection

Sourdive

Altman

Zajac

et al. 1998

The Journal of Experimental Medicine

207

135

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Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majority of the expanded CD8 T cells undergo apoptosis, leaving behind a stable number of memory cells. The relationship between the CD8 T cells that clear the acute viral infection and the long-lived CD8 memory pool remaining in the individual is not fully understood. To address this issue, we examined the T cell receptor (TCR) repertoire of virus-specific CD8 T cells in the mouse model of infection with lymphocytic choriomeningitis virus (LCMV) using three approaches: (a) in vivo quantitative TCR β chain V segment and complementarity determining region 3 (CDR3) length repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV-specific CD8 T cells with MHC class I tetramers containing viral peptide and costaining with TCR Vβ–specific antibodies; and (c) functional TCR fingerprinting based on recognition of variant peptides. We compared the repertoire of CD8 T cells responding to acute primary and secondary LCMV infections, together with that of virus-specific memory T cells in immune mice. Our analysis showed that CD8 T cells from several Vβ families participated in the anti-LCMV response directed to the dominant cytotoxic T lymphocyte (CTL) epitope (NP118–126). However, the bulk (∼70%) of this CTL response was due to three privileged T cell populations systematically expanding during LCMV infection. Approximately 30% of the response consisted of Vβ10+ CD8 T cells with a β chain CDR3 length of nine amino acids, and 40% consisted of Vβ8.1+ (β CDR3 = eight amino acids) and Vβ8.2+ cells (β CDR3 = six amino acids). Finally, we showed that the TCR repertoire of the primary antiviral CD8 T cell response was similar both structurally and functionally to that of the memory pool and the secondary CD8 T cell effectors. These results suggest a stochastic selection of memory cells from the pool of CD8 T cells activated during primary infection.

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“…Bachmann et al examined the response to 16 single aa-variants of an ID determinant from lymphocytic choriomeningitis virus (LCMV) and found that the secondary response (analysed ex vivo) was purged of a number of cross-reactivities that were present in the primary response, suggesting a functional maturation towards high affinity clones. 121 Higher avidity of secondary T cells were also found after in vitro stimulation. 122 This agrees with findings in a class II-restricted system, of a preferential loss of TCR with the fastest off-rates for the nominal antigen.…”

Section: Cross-reactivity In T-cell Responsesmentioning

confidence: 95%

Cross‐reactivity in T‐cell antigen recognition

Regner

2001

Immunol Cell Biol

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The molecular interactions between the T-cell receptor (TCR) and peptide-MHC (pMHC) have been elucidated in recent years. Nevertheless, the fact that binding of only slightly different ligands by a TCR, or ligation of the same pMHC at different developmental stages of the T cell, can have opposing consequences, continues to pose intellectual challenges. Kinetic proofreading models, which have at their core the dissociation rates of pMHC from the TCR, are best suited to account for these observations. However, T cells can be triggered by peptides with often minimal homology to the primary immunogenic peptide. This cross-reactivity of the TCR is manifest at several levels, from positive selection of immature thymocytes to homeostasis and antigen-cross- reactive immune responses of mature peripheral T cells. The implications of the high cross-reactivity of T-cell antigen recognition for self-tolerance and T-cell memory are discussed.

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Functional management of an antiviral cytotoxic T-cell response

Cited by 61 publications

References 39 publications

Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection

Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection

Conserved T Cell Receptor Repertoire in Primary and Memory CD8 T Cell Responses to an Acute Viral Infection

Cross‐reactivity in T‐cell antigen recognition

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