Peptide-induced proliferation and lymphokine production in human T cells in the absence of antigen-presenting cells: Role of T-cell activation state and costimulatory signals

1992 ◽  
Vol 34 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Esteban Celis ◽  
Joseph J. Goodwin ◽  
Toshiji Saibara
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Lymphokine Production ◽  
Human T Cells ◽  
Costimulatory Signals ◽  
Antigen Presenting

scholarly journals Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

1998 ◽  
Vol 187 (10) ◽  
pp. 1611-1621 ◽  
Author(s):  
Sarah E. Townsend ◽  
Christopher C. Goodnow
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Cell Fate ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.

scholarly journals The second touch hypothesis: T cell activation, homing and polarization

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 37 ◽  
Author(s):  
Klaus Ley
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Cell Interaction ◽  
Cell Polarization ◽  
Antigen Presenting ◽  
Inflamed Tissue

The second touch hypothesis states that T cell activation, proliferation, induction of homing receptors and polarization are distinguishable and, at least in part, sequential. The second touch hypothesis maintains that full T cell polarization requires T cell interaction with antigen-presenting cells (DCs, macrophages, B cells and certain activated stromal cells) in the non-lymphoid tissue where the antigen resides. Upon initial antigen encounter in peripheral lymph nodes (PLN), T cells become activated, proliferate and express homing receptors that enable them to recirculate to the (inflamed) tissue that contains the antigen. Differentiation into the T helper lineages Th1, Th2, Th17 and induced regulatory T cells (iTreg) requires additional antigen presentation by tissue macrophages and other antigen presenting cells (APCs) in the inflamed tissue. Here, I present a conceptual framework for the importance of peripheral (non-lymphoid) antigen presentation to antigen-experienced T cells.

scholarly journals Augmentation of T-cell activation by oscillatory forces and engineered antigen-presenting cells

2019 ◽  
Author(s):  
Fatemeh S. Majedi ◽  
Mohammad Mahdi Hasani-Sadrabadi ◽  
Timothy J. Thauland ◽  
Song Li ◽  
Louis-S. Bouchard ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Signal Strength ◽  
Antigen Presenting Cells ◽  
Oscillatory Movement ◽  
Antigen Presenting ◽  
The Impact

AbstractActivation of T cells by antigen presenting cells allows them to proliferate, produce cytokines, and kill infected or cancerous cells. We and others have shown that T cell receptors receive and in fact require mechanical forces from their own movements and the movements of antigen presenting cells. Emulation of T cell activation in vitro allows for the massive expansion of T cells necessary for clinical applications. In this paper, we studied the impact of augmenting novel artificial antigen presenting cells of various sizes and antigenic signal strength with mechanical, oscillatory movement. We showed that dynamic culture roughly doubles signal strength as compared to conventional, static culture. We demonstrated that tuning the strength of signal to a “sweet spot” allows for robust expansion of induced regulatory T cells, which is impeded by approaches that simply maximize activation.

T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease By Regulating Hematopoietic Antigen Presenting Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 846-846
Author(s):  
Jianing Fu ◽  
Yongxia Wu ◽  
Hung Nguyen ◽  
Jessica Lauren Heinrichs ◽  
Steven Schutt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Apoptosis ◽  
Cell Activation ◽  
T Cell Apoptosis ◽  
Donor T Cells ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract Graft-versus-host disease (GVHD) remains to be a major obstacle for the efficacy and continuing success of allogeneic hematopoietic stem cell transplantation in the treatment of various malignant and non-malignant diseases. Activation of antigen presenting cells (APCs), both host and donor origin, plays a crucial role in priming alloreactive donor T cells to induce and intensify acute GVHD (aGVHD). Beyond its critical effects on T cells, the T-box transcription factor T-bet also regulates activity of APCs, including dendritic cells (DCs) and B cells. However, the effect and mechanism of T-bet in regulating APCs in the development of aGVHD has not been investigated. To evaluate the role of T-bet in modulating APC function and aGVHD development, we compared the severity of aGVHD in WT versus T-bet-/- recipients using several well-defined, clinically relevant murine models of allogeneic bone marrow transplantation (allo-BMT). We observed that T-bet-/- recipients developed much milder aGVHD than their WT counterparts, reflected by significantly higher rate of survival, lower clinical scores, and better donor BM-derived B- and T-cell reconstitution. In T-bet-/- recipients, donor T cells significantly reduced IFN-γ production, proliferation and migration, and caused less damage in aGVHD target organs, such as liver and gut. By using various BM chimeras as the recipients, we further observed that T-bet expressed on recipient hematopoietic APCs was primarily responsible for donor T-cell response and pathogenicity in causing aGVHD. Additionally, we evaluated the role of T-bet in donor APCs by transplanting WT or T-bet-/- BM together with WT T cells into lethally irradiated allogeneic recipients. We observed that recipients of T-bet-/- BM developed attenuated aGVHD compared with those of WT BM, suggesting that T-bet also contributes to the function of donor APCs in the induction of GVHD. Given DCs are the most potent hematopoietic APCs, we subsequently focused on recipient DCs. DCs in T-bet-/- recipient produced less IFN-γ, expressed higher levels of Trail, but not FasL or TNF, to induce significantly higher levels of apoptosis on donor T cells prior to their massive proliferation. To test whether Trail/DR5 interaction is responsible for the induction of donor T cell apoptosis and subsequent reduction of aGVHD in T-bet-/- recipients, we compared the ability of WT or DR5-/- T cells in inducing aGVHD in WT versus T-bet-/- recipients after allo-BMT. While WT T cells induced severe aGVHD in WT recipients, they failed to do in T-bet-/- recipients. In contrast, DR5-/- donor T cells were capable to induce severe aGVHD in the recipients regardless of T-bet expression. These data suggests that Trail/DR5 interaction is a major signaling pathway responsible for donor T-cell apoptosis induced by T-bet-/- APCs, through which alleviates the development of aGVHD. In conclusion, we demonstrate that T-bet up-regulates IFN-γ production and down-regulates Trail expression on recipient DCs, which promotes donor T-cell activation and mitigates T-cell apoptosis, respectively. Thus, T-bet plays a critical role in the development of aGVHD by regulating the activity of hematopoietic APCs, particularly DCs. Taken together with our previous findings, we propose that T-bet is a potential therapeutic target for the control of aGVHD through regulating T-cell activation and differentiation as well as APC functions. Disclosures No relevant conflicts of interest to declare.

scholarly journals Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jinar Rostami ◽  
Grammatiki Fotaki ◽  
Julien Sirois ◽  
Ropafadzo Mzezewa ◽  
Joakim Bergström ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Human Microglia ◽  
Mhc Ii ◽  
Human Astrocytes ◽  
Antigen Presenting

Abstract Background Many lines of evidence suggest that accumulation of aggregated alpha-synuclein (αSYN) in the Parkinson’s disease (PD) brain causes infiltration of T cells. However, in which ways the stationary brain cells interact with the T cells remain elusive. Here, we identify astrocytes as potential antigen-presenting cells capable of activating T cells in the PD brain. Astrocytes are a major component of the nervous system, and accumulating data indicate that astrocytes can play a central role during PD progression. Methods To investigate the role of astrocytes in antigen presentation and T-cell activation in the PD brain, we analyzed post mortem brain tissue from PD patients and controls. Moreover, we studied the capacity of cultured human astrocytes and adult human microglia to act as professional antigen-presenting cells following exposure to preformed αSYN fibrils. Results Our analysis of post mortem brain tissue demonstrated that PD patients express high levels of MHC-II, which correlated with the load of pathological, phosphorylated αSYN. Interestingly, a very high proportion of the MHC-II co-localized with astrocytic markers. Importantly, we found both perivascular and infiltrated CD4+ T cells to be surrounded by MHC-II expressing astrocytes, confirming an astrocyte T cell cross-talk in the PD brain. Moreover, we showed that αSYN accumulation in cultured human astrocytes triggered surface expression of co-stimulatory molecules critical for T-cell activation, while cultured human microglia displayed very poor antigen presentation capacity. Notably, intercellular transfer of αSYN/MHC-II deposits occurred between astrocytes via tunneling nanotubes, indicating spreading of inflammation in addition to toxic protein aggregates. Conclusions In conclusion, our data from histology and cell culture studies suggest an important role for astrocytes in antigen presentation and T-cell activation in the PD brain, highlighting astrocytes as a promising therapeutic target in the context of chronic inflammation.

scholarly journals The second touch hypothesis: T cell activation, homing and polarization

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 37 ◽  
Author(s):  
Klaus Ley
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Cell Interaction ◽  
Cell Polarization ◽  
Antigen Presenting ◽  
Inflamed Tissue

The second touch hypothesis states that T cell activation, proliferation, induction of homing receptors and polarization are distinguishable and, at least in part, sequential. The second touch hypothesis maintains that full T cell polarization requires T cell interaction with antigen-presenting cells (DCs, macrophages, B cells and certain activated stromal cells) in the non-lymphoid tissue where the antigen resides. Upon initial antigen encounter in peripheral lymph nodes (PLN), T cells become activated, proliferate and express homing receptors that enable them to recirculate to the (inflamed) tissue that contains the antigen. Differentiation into the T helper lineages Th1, Th2, Th17 and induced regulatory T cells (iTreg) requires additional antigen presentation by tissue macrophages and other antigen presenting cells (APCs) in the inflamed tissue. Here, I present a conceptual framework for the importance of peripheral (non-lymphoid) antigen presentation to antigen-experienced T cells.

scholarly journals Mesangial Cells Exhibit Features of Antigen-Presenting Cells and Activate CD4+ T Cell Responses

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hongyu Yu ◽  
Shaoyuan Cui ◽  
Yan Mei ◽  
Qinggang Li ◽  
Lingling Wu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mesangial Cells ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Antigen Presenting

Background. Mesangial cells play a prominent role in the development of inflammatory diseases and autoimmune disorders of the kidney. Mesangial cells perform the essential functions of helping to ensure that the glomerular structure is stable and regulating capillary flow, and activated mesangial cells acquire proinflammatory activities. We investigated whether activated mesangial cells display immune properties and control the development of T cell immunity. Methods. Flow cytometry analysis was used to study the expression of antigen-presenting cell surface markers and costimulatory molecules in mesangial cells. CD4+ T cell activation induced by mesangial cells was detected in terms of T cell proliferation and cytokine production. Results. IFN-γ-treated mesangial cells express membrane proteins involved in antigen presentation and T cell activation, including MHC-II, ICAM-1, CD40, and CD80. This finding suggests that activated mesangial cells can take up and present antigenic peptides to initiate CD4+ T cell responses and thus act as nonprofessional antigen-presenting cells. Polarization of naïve CD4+ T cells (Th0 cells) towards the Th1 phenotype was induced by coculture with activated mesangial cells, and the resulting Th1 cells showed increased mRNA and protein expression of inflammation-associated genes. Conclusion. Mesangial cells can present antigen and modulate CD4+ T lymphocyte proliferation and differentiation. Interactions between mesangial cells and T cells are essential for sustaining the inflammatory response in a variety of glomerulonephritides. Therefore, mesangial cells might participate in immune function in the kidney.

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