CD8 T cell priming by B lymphocytes is CD4 help dependent

Castiglioni, Paola; Gerloni, Mara; Cortez-Gonzalez, Xochitl; Zanetti, Maurizio

doi:10.1002/eji.200425530

Cited by 29 publications

(25 citation statements)

References 54 publications

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“…Accordingly, we found that DCprimed CTLs expressed higher levels of key cytotoxic mediators (granzyme B and IFN-γ), and upstream master regulators (T-bet, EOMES, and BLIMP-1) ( Figure 1B). Killing deficiencies observed in B cell priming were previously reported to result from impaired granzyme B expression and increased activation-induced T cell death (AICD) (41,42), which could be overcome by IL-15 and IL-21 (43,44). Consistent with earlier reports (41)(42)(43)(44), the addition of exogenous IL-15 and IL-21 during B cell priming partially rescued granzyme B expression (Supplemental Figure 1C) and AICD (Supplemental Figure 1D) in CTLs.…”

Section: Resultssupporting

confidence: 88%

Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression

Lin¹,

Chen²,

Chen³

et al. 2014

J. Clin. Invest.

113

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Section: Resultssupporting

confidence: 88%

Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression

Lin¹,

Chen²,

Chen³

et al. 2014

J. Clin. Invest.

113

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“…6), we conclude that Th-Th cooperation was key to overcome the subimmunogenicity of the -VTSA-determinant in both wild-type mice and MUC.1-Tg mice. Furthermore, the activation of CD8 T cells against the 9-mer -VTSA-peptide fits within the framework of a model in which activation of CD8 T cells by Ag-presenting B lymphocytes is Th dependent (38). Collectively, our data and interpretation of the phenomenon suggest that the immunological switch that hallmarks functionally Th-Th cooperation is the property of the APC (a B lymphocyte) where inducible costimulation plays a critical role.…”

Section: Discussionsupporting

confidence: 58%

The Cooperation between Two CD4 T Cells Induces Tumor Protective Immunity in MUC.1 Transgenic Mice

Gerloni

Castiglioni

Zanetti

2005

The Journal of Immunology

Self Cite

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Immunity and tumor protection in mice transgenic for human MUC.1, a glycoprotein expressed in the majority of cancers of epithelial origin in humans, were induced by vaccination with B lymphocytes genetically programmed to activate MUC.1-specific CD4 T cells. Their activation required a functional cooperation between two Th cells, one specific for a self (MUC.1) and the other for a nonself T cell determinant. The immunological switch provided by Th-Th cooperation was sufficient to induce MUC.1-specific CD4 and CD8 T cell responses in MUC.1-transgenic mice, and protect them permanently from tumor growth. CD4 T cells specific for MUC.1 lacked cytolytic function, but produced IFN-γ upon restimulation with Ag. We conclude that immunity against tumor self-Ags and tumor protection can be regulated exploiting an inherent property of the immune system.

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“…There may be other cell-cell interactions that may be important during insulitis, for example the role of CD4+ cells in the activation of CD8+ cells (Castiglioni et al, 2005). Even restricting the model to the two immune cell types described in this manuscript, we could consider different clonal populations of the T cells (Khadra et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Dynamics of Insulitis in Human Type 1 Diabetes

et al. 2016

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Type 1 diabetes (T1D) is an auto-immune disease characterized by the selective destruction of the insulin secreting beta cells in the pancreas during an inflammatory phase known as insulitis. Patients with T1D are typically dependent on the administration of externally provided insulin in order to manage blood glucose levels. Whilst technological developments have significantly improved both the life expectancy and quality of life of these patients, an understanding of the mechanisms of the disease remains elusive. Animal models, such as the NOD mouse model, have been widely used to probe the process of insulitis, but there exist very few data from humans studied at disease onset. In this manuscript, we employ data from human pancreases collected close to the onset of T1D and propose a spatio-temporal computational model for the progression of insulitis in human T1D, with particular focus on the mechanisms underlying the development of insulitis in pancreatic islets. This framework allows us to investigate how the time-course of insulitis progression is affected by altering key parameters, such as the number of the CD20+ B cells present in the inflammatory infiltrate, which has recently been proposed to influence the aggressiveness of the disease. Through the analysis of repeated simulations of our stochastic model, which track the number of beta cells within an islet, we find that increased numbers of B cells in the peri-islet space lead to faster destruction of the beta cells. We also find that the balance between the degradation and repair of the basement membrane surrounding the islet is a critical component in governing the overall destruction rate of the beta cells and their remaining number. Our model provides a framework for continued and improved spatio-temporal modeling of human T1D.

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CD8 T cell priming by B lymphocytes is CD4 help dependent

Cited by 29 publications

References 54 publications

Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression

Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression

The Cooperation between Two CD4 T Cells Induces Tumor Protective Immunity in MUC.1 Transgenic Mice

Spatiotemporal Dynamics of Insulitis in Human Type 1 Diabetes

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