Termination of T cell priming relies on a phase of unresponsiveness promoting disengagement from APCs and T cell division

Bohineust, Armelle; Garcia, Zacarias; Beuneu, Hélène; Lemaı̂tre, Fabrice; Bousso, Philippe

doi:10.1084/jem.20171708

Cited by 21 publications

(21 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with disengagement of primed T cells from DCs just prior to the commencement of division, i.e. the end of pre-mitotic phase (Bohineust et al, 2018). We further confirmed the presence of endogenous PMCs by flow cytometry ( Figure 4D).…”

Section: Pmcs Kill Conventional Dcs In a Granzyme-b Dependent Mannersupporting

confidence: 86%

See 1 more Smart Citation

Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection

Dandamudi

Blair

Arifa

et al. 2018

Preprint

View full text Add to dashboard Cite

Granzyme B mRNA is expressed in primed CD8 T cells within 12 hours, but the consequences of this for the immune response are unknown. We observed that substantial portion of the naïve CD8 T cell repertoire expressed granzyme B and became pre-mitotic cytotoxic cells (PMCs) immediately in response to Listeria monocytogenes or Lymphocytic choriomeningitis virus infections. The surprising breadth arose from sufficiency of low potency peptide-MHC to induce granzyme B expression in the context of infection. PMCs killed antigen bearing dendritic cells (DCs) in a granzyme B-dependent but largely perforinindependent fashion between 1-2 days post infection. This terminated antigen presentation at 3 days and resulted in reduced clonal expansion. As additional consequences, we highlight that PMCs reduced the burden of DC-borne infectious agents, but also opened a window of vulnerability for secondary infection. Thus, PMCs serve antigen-specific, regulatory and host defence functions, that are innate-like in scale, at the onset of the adaptive immune response.

show abstract

Section: Pmcs Kill Conventional Dcs In a Granzyme-b Dependent Mannersupporting

confidence: 86%

“…Actively dividing CD8 T cells do not make contacts with antigen presenting DCs (Bohineust et al, 2018) and once the division starts, they divide every 4-6 hours (Zhang and Bevan, 2011). Thus, PMCs are able to release their granzyme B into DCs only during the pre-mitotic phase.…”

Section: Discussionmentioning

confidence: 99%

Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection

Dandamudi

Blair

Arifa

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Maintenance of the immune synapse is known to be influenced by T cell-intrinsic factors such as the strength of TCR signaling (Henrickson et al, 2008;Bohineust et al, 2018). However, the processes downstream of the cellular migration machinery that enable the transition from an arrested to a motile state are not clear (Hugues et al, 2004;Celli et al, 2007;Skokos et al, 2007;Shulman et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact

et al. 2020

View full text Add to dashboard Cite

When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact.

show abstract

“…In contrast, we show that the focimediated synapse retention is independent of intracellular calcium because BAPTA treatment did not reduce foci or promote synapse symmetry breaking. Detachment of T cells from APCs was shown to be associated with a period of TCR signaling unresponsiveness (Bohineust et al, 2018); whether a reduction in TCR -induced calcium signaling during the transition from stable to motile synaptic interface might play a role in antigen unresponsiveness remains to be investigated. It is important to note that the methodology we used to examine the foci-intracellular calcium connection using pharmacological calcium elevation can generate minor off-target effects on contact symmetry and actin foci, since they alter some basic features of the synapse (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Maintenance of the immune synapse is known to be influenced by T cell-intrinsic factors such as the strength of TCR signaling (Bohineust et al, 2018;Henrickson et al, 2008), however the downstream mechanisms at the level of the cellular migration machinery that enact the transition from an arrested to a motile state are not clear (Celli et al, 2007;Hugues et al, 2004;Shulman et al, 2014;Skokos et al, 2007). One of the ways in which the TCR-associated actin dynamics could enforce synapse symmetry and stability is by regulating mechanical forces within the synapse.…”

Section: Introductionmentioning

confidence: 99%

Cytoskeletal tension actively sustains the migratory T cell synaptic contact

Kumari

Mak

Poh

et al. 2018

Preprint

View full text Add to dashboard Cite

When migratory T cells encounter antigen presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T cell immunity. While the cellular processes underlying synapse formation have been well-characterized, those that maintain the symmetry, and thereby the stability of the synapse remain unknown. Here we identify an antigen-triggered mechanism that actively promotes T cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott -Aldrich syndrome Protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T cell activation, WASP is degraded, leading to cytoskeletal rearrangement and tension decay, which result in synapse breaking.Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell-APC synaptic contact.

show abstract

Termination of T cell priming relies on a phase of unresponsiveness promoting disengagement from APCs and T cell division

Abstract: Bohineust et al. establish that recently activated T cells exhibit a phase of unresponsiveness associated with a defect in calcium entry. This stage was essential to terminate priming, distracting T cells from APCs, and favoring their clonal expansion.

Cited by 21 publications

References 41 publications

Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection

Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection

Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact

Cytoskeletal tension actively sustains the migratory T cell synaptic contact

Contact Info

Product

Resources

About