Class II-Restricted CD8s: New Lessons Violate Old Paradigms

Migueles, Stephen A.; Connors, Mark

doi:10.1016/j.immuni.2016.10.004

Cited by 6 publications

(5 citation statements)

References 9 publications

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“…In cases as in controls, AIM reactivity was most often detected concomitantly in the CD4 + and CD8 + T-cell compartments ( Fig 2C ). Although Ag1 stimulation was supposed to be specific for CD4 + T cells according to the manufacturer, we actually found that Ag1 also activated CD8 + T cells, in agreement with other authors’ observations [ 20 ], possibly due to further processing of peptides by circulating antigen-presenting cells [ 20 ] or to the expansion of unconventional MHC-II-restricted CD8 + T-cell clones [ 21 , 22 ]. In fact, AIM + T cells were most often detected concomitantly in CD4 + and CD8 + compartments for both Ag1 and Ag2 stimulations, even though Ag1 stimulation resulted in non-significantly higher proportions of AIM + T cells in the CD4 + compartment only compared to Ag2 stimulation ( Fig 2D ).…”

Section: Resultssupporting

confidence: 92%

Assessing SARS-CoV-2-specific T-cell reactivity in late convalescents and vaccinees: Comparison and combination of QuantiFERON and activation-induced marker assays, and relation with antibody status

Gatti

Zizzo²,

Paschale

et al. 2023

PLoS ONE

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Objectives Monitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON™ (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees). Methods Twenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-γ) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4+CD25+CD134+, CD4+CD69+CD137+ and CD8+CD69+CD137+ T-cell frequencies were measured by flow cytometry. Results In convalescents, substantial agreement was observed between QFN and AIM assays. IFN-γ concentrations and AIM+ (CD69+CD137+) CD4+ T-cell frequencies correlated with each other, with Ab levels and AIM+ CD8+ T-cell frequencies, whereas AIM+ (CD25+CD134+) CD4+ T-cell frequencies correlated with age. AIM+ CD4+ T-cell frequencies increased with time since infection, whereas AIM+ CD8+ T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees. Conclusions Albeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (TH1)-reactive (QFNpos AIMpos Abshigh), non-TH1-reactive (QFNneg AIMpos Abshigh/low), and pauci-reactive (QFNneg AIMneg Abslow).

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Section: Resultssupporting

confidence: 92%

Assessing SARS-CoV-2-specific T-cell reactivity in late convalescents and vaccinees: Comparison and combination of QuantiFERON and activation-induced marker assays, and relation with antibody status

Gatti

Zizzo²,

Paschale

et al. 2023

PLoS ONE

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“…A question that arises from our results is how TCR specificity impacts on CD4-derived CD8 T cells. Antigen-restricted MHC class II-specific CD8 + T cells have been described in HIVinfected patients (38)(39)(40). Moreover, a recent study reports the in vivo generation of a CD4−CD8ab + MHC II-recognizing lineage from effector CD4 + T cells using murine models of acute infection (41).…”

Section: Discussionmentioning

confidence: 99%

Human CD4 T Cells From Thymus and Cord Blood Are Convertible Into CD8 T Cells by IL-4

et al. 2022

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Commitment to the CD4+ or CD8+ T cell lineages is linked to the acquisition of a functional program broadly defined by helper and cytotoxic properties, respectively. The mechanisms underlying these processes in the human thymus remain largely unclear. Moreover, recent thymic emigrants are thought to have some degree of plasticity, which may be important for the shaping of the immune system and adjustment to specific peripheral needs. We show here that IL-4 induces proliferation-independent de novo synthesis of CD8αβ in human CD4 single-positive (SP) thymocytes, generating a stable CD8SP population that features a diverse TCRαβ repertoire, CD4 expression shut-down and ThPOK downregulation. IL-4 also promotes an innate-like program in both CD4SP and CD8SP thymocytes, characterized by Eomes upregulation in the absence of T-bet, in line with its recognized role in the generation of thymic innate-like CD8+ T cells. The clinical relevance of these findings is further supported by the profile of IL-4 production and IL-4 receptor expression that we identified in the human thymus. Importantly, human cord blood CD4+ T cells preserve the ability to generate Eomes+ CD8+ T cells in the presence of IL-4, with implications in neonatal immunity. Our results support a role for IL-4 in the dynamic regulation of human thymocyte plasticity and identify novel strategies to modulate immune responses.

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“…Several of the genes differentially expressed within this pathway were shared between mice and humans, including multiple MHC complexes, CD74, which stabilizes MHC II molecules (33), and HSPs, which are critical modulators of effector response after antigen presentation (34,35). B cells present antigens via MHC II molecules to CD4 T cells and, under specific conditions CD8 T cells (36,37), resulting in T cell activation. Prior murine data have implicated CD4 T cells and CD8 T cells in adverse cardiac remodeling following myocardial injury (38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure

Lovell,

Duque,

Rousseau

et al. 2024

Preprint

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Cardiovascular disease remains the leading cause of death worldwide. A primary driver of cardiovascular mortality is ischemic heart failure, a form of cardiac dysfunction that develops in patients who survive myocardial infarction. Acute cardiac damage triggers robust changes in the spleen with rapid migration of immune cells from the spleen to the heart. Activating this cardio-splenic axis contributes to progressive cardiac dysfunction. The cardio-splenic axis has, therefore, been identified as a promising therapeutic target to prevent or treat heart failure. However, our understanding of the precise mechanisms by which specific immune cells contribute to adverse cardiac remodeling within the cardio-splenic axis remains limited. Here, we show that splenic B cells contribute to the development of heart failure via MHC II-mediated antigen presentation. We found that the transfer of splenic B cells from mice with ischemic heart failure promoted adverse cardiac remodeling and splenic inflammatory changes in naive recipient mice. Based on single-cell RNA sequencing analysis of splenic B cells from mice with ischemic heart failure, we hypothesized that B cells contributed to adverse cardiac remodeling through antigen presentation by MHC II molecules. This mechanism was confirmed using transgenic mice with B cell-specific MHC II deletion and by analyzing circulating B cells from humans who experienced myocardial infarction. Our results broaden our understanding of B lymphocyte biology, reshape current models of immune activation in response to cardiac injury, and point towards MHC II-mediated signaling in B cells as a novel and specific therapeutic target in chronic heart failure.

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Class II-Restricted CD8s: New Lessons Violate Old Paradigms

Abstract: CD8+ T cells that recognize peptides presented by MHC class II molecules have been observed in a macaque SIV vaccine model. A new study by Ranasinghe et al. (2016) shows that virus-specific class-II-restricted CD8+ T cells can be found in some HIV-infected patients.

Cited by 6 publications

References 9 publications

Assessing SARS-CoV-2-specific T-cell reactivity in late convalescents and vaccinees: Comparison and combination of QuantiFERON and activation-induced marker assays, and relation with antibody status

Assessing SARS-CoV-2-specific T-cell reactivity in late convalescents and vaccinees: Comparison and combination of QuantiFERON and activation-induced marker assays, and relation with antibody status

Human CD4 T Cells From Thymus and Cord Blood Are Convertible Into CD8 T Cells by IL-4

B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure

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