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1.
Cells ; 13(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38727273

ABSTRACT

Bovine Th2 cells have usually been characterized by IL4 mRNA expression, but it is unclear whether their IL4 protein expression corresponds to transcription. We found that grass-fed healthy beef cattle, which had been regularly exposed to parasites on the grass, had a low frequency of IL4+ Th2 cells during flow cytometry, similar to animals grown in feedlots. To assess the distribution of IL4+ CD4+ T cells across tissues, samples from the blood, spleen, abomasal (draining), and inguinal lymph nodes were examined, which revealed limited IL4 protein detection in the CD4+ T cells across the examined tissues. To determine if bovine CD4+ T cells may develop into Th2 cells, naïve cells were stimulated with anti-bovine CD3 under a Th2 differentiation kit in vitro. The cells produced primarily IFNγ proteins, with only a small fraction (<10%) co-expressing IL4 proteins. Quantitative PCR confirmed elevated IFNγ transcription but no significant change in IL4 transcription. Surprisingly, GATA3, the master regulator of IL4, was highest in naïve CD4+ T cells but was considerably reduced following differentiation. To determine if the differentiated cells were true Th2 cells, an unbiased proteomic assay was carried out. The assay identified 4212 proteins, 422 of which were differently expressed compared to those in naïve cells. Based on these differential proteins, Th2-related upstream components were predicted, including CD3, CD28, IL4, and IL33, demonstrating typical Th2 differentiation. To boost IL4 expression, T cell receptor (TCR) stimulation strength was reduced by lowering anti-CD3 concentrations. Consequently, weak TCR stimulation essentially abolished Th2 expansion and survival. In addition, extra recombinant bovine IL4 (rbIL4) was added during Th2 differentiation, but, despite enhanced expansion, the IL4 level remained unaltered. These findings suggest that, while bovine CD4+ T cells can respond to Th2 differentiation stimuli, the bovine IL4 pathway is not regulated in the same way as in mice and humans. Furthermore, Ostertagia ostertagi (OO) extract, a gastrointestinal nematode in cattle, inhibited signaling via CD3, CD28, IL4, and TLRs/MYD88, indicating that external pathogens can influence bovine Th2 differentiation. In conclusion, though bovine CD4+ T cells can respond to IL4-driven differentiation, IL4 expression is not a defining feature of differentiated bovine Th2 cells.


Subject(s)
Cell Differentiation , Th2 Cells , Animals , Cattle , Th2 Cells/immunology , Th2 Cells/metabolism , Interleukin-4/metabolism , GATA3 Transcription Factor/metabolism , GATA3 Transcription Factor/genetics , Interferon-gamma/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism
2.
Nano Lett ; 24(18): 5513-5520, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38634689

ABSTRACT

P-type self-doping is known to hamper tin-based perovskites for developing high-performance solar cells by increasing the background current density and carrier recombination processes. In this work, we propose a gradient homojunction structure with germanium doping that generates an internal electric field across the perovskite film to deplete the charge carriers. This structure reduces the dark current density of perovskite by over 2 orders of magnitude and trap density by an order of magnitude. The resultant tin-based perovskite solar cells exhibit a higher power conversion efficiency of 13.3% and excellent stability, maintaining 95% and 85% of their initial efficiencies after 250 min of continuous illumination and 3800 h of storage, respectively. We reveal the homojunction formation mechanism using density functional theory calculations and molecular level characterizations. Our work provides a reliable strategy for controlling the spatial energy levels in tin perovskite films and offers insights into designing intriguing lead-free perovskite optoelectronics.

3.
Adv Mater ; : e2313524, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38453665

ABSTRACT

Crystallization orientation plays a crucial role in determining the performance and stability of perovskite solar cells (PVSCs), whereas effective strategies for realizing oriented perovskite crystallization is still lacking. Herein, a facile and efficient top-down strategy is reported to manipulate the crystallization orientation via treating perovskite wet film with propylamine chloride (PACl) before annealing. The PA+ ions tend to be adsorbed on the (001) facet of the perovskite surface, resulting in the reduced cleavage energy to induce (001) orientation-dominated growth of perovskite film and then reduce the temperature of phase transition, meanwhile, the penetrating Cl ions further regulate the crystallization process. As-prepared (001)-dominant perovskite films exhibit the ameliorative film homogeneity in terms of vertical and horizontal scale, leading to alleviated lattice mismatch and lowered defect density. The resultant PVSC devices deliver a champion power conversion efficiency (PCE) of 25.07% with enhanced stability, and the unencapsulated PVSC device maintains 95% of its initial PCE after 1000 h of operation at the maximum power point under simulated AM 1.5G illumination.

4.
Nat Commun ; 15(1): 1066, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38316825

ABSTRACT

Presynthesized perovskite quantum dots are very promising for making films with different compositions, as they decouple crystallization and film-formation processes. However, fabricating large-area uniform films using perovskite quantum dots is still very challenging due to the complex fluidic dynamics of the solvents. Here, we report a robust film-formation approach using an environmental-friendly binary-solvent strategy. Nonbenzene solvents, n-octane and n-hexane, are mixed to manipulate the fluidic and evaporation dynamics of the perovskite quantum dot inks, resulting in balanced Marangoni flow, enhanced ink spreadability, and uniform solute-redistribution. We can therefore blade-coat large-area uniform perovskite films with different compositions using the same fabrication parameters. White and red perovskite light-emitting diodes incorporating blade-coated films exhibit a decent external quantum efficiency of 10.6% and 15.3% (0.04 cm2), and show a uniform emission up to 28 cm2. This work represents a significant step toward the application of perovskite light-emitting diodes in flat panel solid-state lighting.

5.
Adv Mater ; 36(8): e2309921, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38016083

ABSTRACT

Metal halide perovskite light-emitting diodes (PeLEDs) are attracting increasing attention due to their potential applications in flat panel lighting and displays. The solution process, large-area fabrication, and flexibility are attractive properties of PeLEDs over traditional inorganic LEDs. However, it is still very challenging to deposit uniform perovskite films on flexible substrates using a blade or slot-die coating, as the flexible substrate is not perfectly flat. Here, the inkjet printing technique is adopted, and the key challenges are overcome step-by-step in preparing large-area films on flexible substrates. Double-hole transporting layers are first used and a wetting interfacial layer to improve the surface wettability so that the printed perovskite droplets can form a continuous wet film. The fluidic and evaporation dynamics of the perovskite wet layer is manipulated to suppress the coffee ring effect by solvent engineering. Uniform perovskite films are obtained finally on flexible substrates with different perovskite compositions. The peak external quantum efficiency of the inkjet-printed PeLEDs reaches 14.3%. Large-area flexible PeLEDs (4 × 7 cm2 ) also show very uniform emission. This work represents a significant step toward real applications of large-area PeLEDs in flexible flat-panel lighting.

6.
Opt Express ; 31(24): 39638-39646, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38041280

ABSTRACT

In this work, periodic rectangular arrays were fabricated on quartz substrates using the femtosecond laser ablation technique, on which inorganic cesium lead bromide thin films were grown using the spin coating method. Enhanced photoluminescence emission was investigated using a homebuilt confocal microscope, and increased light absorption due to the engineered structures was also measured. High-performance amplified spontaneous emission with typical narrow lasing emission peaks excited using a nanosecond laser centered at 266 nm was obtained. This work provides a method to modify the performance of optoelectrical devices, which helps develop light-emitting diodes, photodetectors, solar cells, and lasers.

7.
Nature ; 624(7992): 557-563, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37913815

ABSTRACT

Perovskite solar cells with the formula FA1-xCsxPbI3, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice1,2, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells3,4. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.

8.
Opt Express ; 31(20): 32263-32272, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37859033

ABSTRACT

GaN is a one of promising materials for nonlinear optical applications. In this work, the broadband nonlinear optical response and potential applications for all-optical switching (AOS) are evaluated in low-defect GaN. In the pump-probe experiments, the ultrafast optical switching times are consistent with pulse widths accompanied with relative weak free-carrier absorption response, and the modulation contrast can reach ∼60% by varying the polarization orientations between the pump and probe lights. In the visible region, the broadband two-photon absorption effect exhibits excellent values for the imaginary part of figure of merit (FOM), providing the possibility of AOS based on nonlinear absorption (magnitude). While in the near-infrared region and under the presence of three-photon absorption, not only the real part of FOM based on Kerr effect is evaluated, but also the maximum light intensity for the usage of AOS based on nonlinear refraction (phase) is determined. The broadband nonlinear optical and AOS features in low-defect GaN will be highly favorable for the applications in the field of integrated nonlinear photonics and photonic circuits.

9.
Pathogens ; 12(9)2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37764981

ABSTRACT

Intraepithelial T lymphocytes (T-IELs), which constitute over 50% of the total T lymphocytes in the animal, patrol the mucosal epithelial lining to defend against pathogen invasion while maintaining gut homeostasis. In addition to expressing T cell markers such as CD4 and CD8, T-IELs display T cell receptors (TCR), including either TCRαß or TCRγδ. Both humans and mice share similar T-IEL subsets: TCRγδ+, TCRαß+CD8αα+, TCRαß+CD4+, and TCRαß+CD8αß+. Among these subsets, human T-IELs are predominantly TCRαß+ (over 80%), whereas those in mice are mostly TCRγδ+ (~60%). Of note, the majority of the TCRγδ+ subset expresses CD8αα in both species. Although T-IELs have been extensively studied in humans and mice, their profiles in cattle have not been well examined. Our study is the first to characterize bovine T-IELs using flow cytometry, where we identified several distinct features. The percentage of TCRγδ+ was comparable to that of TCRαß+ T-IELs (both ~50% of CD3+), and the majority of bovine TCRγδ+ T-IELs did not express CD8 (CD8-) (above 60%). Furthermore, about 20% of TCRαß+ T-IELs were CD4+CD8αß+, and the remaining TCRαß+ T-IELs were evenly distributed between CD4+ and CD8αß+ (~40% of TCRαß+ T-IELs each) with no TCRαß+CD8αα+ identified. Despite these unique properties, bovine T-IELs, similar to those in humans and mice, expressed a high level of CD69, an activation and tissue-retention marker, and a low level of CD62L, a lymphoid adhesion marker. Moreover, bovine T-IELs produced low levels of inflammatory cytokines such as IFNγ and IL17A, and secreted small amounts of the immune regulatory cytokine TGFß1. Hence, bovine T-IELs' composition largely differs from that of human and mouse, with the dominance of the CD8- population among TCRγδ+ T-IELs, the substantial presence of TCRαß+CD4+CD8αß+ cells, and the absence of TCRαß+CD8αα+ T-IELs. These results provide the groundwork for conducting future studies to examine how bovine T-IELs respond to intestinal pathogens and maintain the integrity of the gut epithelial barrier in animals.

10.
Adv Mater ; 35(49): e2305946, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37547965

ABSTRACT

Perovskite/organic tandem solar cells (POTSCs) are gaining attention due to their easy fabrication, potential to surpass the S-Q limit, and superior flexibility. However, the low power conversion efficiencies (PCEs) of wide bandgap (Eg) perovskite solar cells (PVSCs) have hindered their development. This work presents a novel and effective mixed-cation passivation strategy (CE) to passivate various types of traps in wide-Eg perovskite. The complementary effect of 4-trifluoro phenethylammonium (CF3 -PEA+ , denoted as CA+ ) and ethylenediammonium (EDA2+ , denoted as EA2+ ) reduces both electron/hole defect densities and non-radiative recombination rate, resulting in a record open-circuit voltage (Voc ) of wide-Eg PVSCs (1.35 V) and a high fill factor (FF) of 83.29%. These improvements lead to a record PCE of 24.47% when applied to fabricated POTSCs, the highest PCE to date. Furthermore, unencapsulated POTSCs exhibit excellent photo and thermal stability, retaining over 90% of their initial PCE after maximum power point (MPP) tracking or exposure to 60 °C for 500 h. These findings imply that the synergic effect of surface passivators is a promising strategy to achieve high-efficiency and stable wide-Eg PVSCs and corresponding POTSCs.

11.
Environ Technol ; 44(5): 659-669, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34657577

ABSTRACT

Micro-nanobubbles can spontaneously generate hydroxyl free radicals (OH). Urea is a cheap reductant and can react with NOx species, and their products are nontoxic and harmless N2, CO2 and H2O. In this study, a Wet Direct Recycling Micro-nanobubble Flue Gas Multi-pollutants Removal System (WDRMRS) was developed for the simultaneous removal of NO, SO2 and Hg0. In this system, a micro-nanobubble generator (MNBG) was used to produce a micro-nanobubble gas-liquid dispersion system (MNBGLS) through recycling the urea solution from the reactor and the simulated flue gas composed of N2, NO, SO2 and Hg0. The MNBGLS, which has a large gas-liquid dispersion interface, was recycled continuously from the MNBG to the reactor, thus achieving cyclic absorption of various pollutants. All of the investigated parameters, including the initial pH and temperature of the absorbent as well as the concentrations of urea, NO and SO2 had significant effects on the NO removal efficiency but did not significantly affect the SO2 removal efficiency, whereas only the initial solution pH and NO concentration affected the Hg0 removal efficiency. The analysis results of the reaction mechanism showed that ·OH played a critical role in the removal of various pollutants. After the treatment by this system, the main removal products were Hg0 sediment, SO42- and NH4+ which could be easily recycled. The use of this system (MNBGLS) for the simultaneous removal of NO, SO2 and Hg0 is a new technology application and research. Recycling process based on MNBGLS succeeded in simultaneously removing NO, SO2 and Hg0. The system (MNBGLS) can provide a reference for commercial applications. The removal products are relatively simple and beneficial to recycling, which can reduce the cost of waste gas treatment.


Subject(s)
Air Pollutants , Environmental Pollutants , Mercury , Sulfur Dioxide , Air Pollutants/analysis , Urea
12.
Angew Chem Int Ed Engl ; 62(5): e202213932, 2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36353929

ABSTRACT

Ion migration is a notorious phenomenon observed in ionic perovskite materials. It causes several severe issues in perovskite optoelectronic devices such as instability, current hysteresis, and phase segregation. Here, we report that, in contrast to lead halide perovskites (LHPs), no ion migration or phase segregation was observed in tin halide perovskites (THPs) under illumination or an electric field. The origin is attributed to a much stronger Sn-halide bond and higher ion migration activation energy (Ea ) in THPs, which remain nearly constant under illumination. We further figured out the threshold Ea for the absence of ion migration to be around 0.65 eV using the CsSny Pb1-y (I0.6 Br0.4 )3 system whose Ea varies with Sn ratios. Our work shows that ion migration does not necessarily exist in all perovskites and suggests metallic doping to be a promising way of stopping ion migration and improving the intrinsic stability of perovskites.

13.
Sci Bull (Beijing) ; 67(1): 54-60, 2022 Jan.
Article in English | MEDLINE | ID: mdl-36545960

ABSTRACT

Substitution of lead (Pb) with tin (Sn) is a very important way to reduce the bandgap of metal halide perovskite for applications in solar cells, and near infrared (NIR) light-emitting diodes (LEDs), etc. However, mixed Pb/Sn perovskite becomes very disordered with high trap density when the Sn molar ratio is less than 20%. This limits the applications of mixed Pb/Sn perovskites in optoelectronic devices such as wavelength tunable NIR perovskite LEDs (PeLEDs). In this work, we demonstrate that alkali cations doping can release the microstrain and passivate the traps in mixed Pb/Sn perovskites with Sn molar ratios of less than 20%, leading to higher carrier lifetime and photoluminescence quantum yield (PLQY). The external quantum efficiency (EQE) of Sn0.2Pb0.8-based NIR PeLEDs is dramatically enhanced from 0.1% to a record value of 9.6% (emission wavelength: 868 nm). This work provides a way of making high quality mixed Pb/Sn optoelectronic devices with small Sn molar ratios.

14.
Adv Mater ; 34(49): e2207180, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36189875

ABSTRACT

The external quantum efficiency (EQE) of state-of-the-art planar-structure perovskite light-emitting diodes (PeLEDs) is mainly limited by the outcoupling efficiency, which is around 20% and decreases significantly with the perovskite thickness. Here, an approach to artificially form textured perovskite films to boost the outcoupling limit of the PeLEDs is reported. By manipulating the dwell time of antisolvents, the perovskite phase precipitation mechanism, film-forming process, and surface texture can be finely controlled. The film surface roughness can be tuned from 15.3 to 241 nm, with haze increasing accordingly from 6% to >90% for films with an average thickness of 1.5 µm. The light outcoupling limit increases accordingly from 11.7% for the flat PeLEDs to 26.5% for the textured PeLEDs due to photon scattering at the interface. Consequently, the EQE is boosted significantly from around 10% to 20.5% with an extraordinarily thick emissive layer of 1.5 µm. This study provides a novel way of forming light-extraction nanostructures for perovskite optoelectronic devices.

15.
Environ Technol ; : 1-10, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-35793811

ABSTRACT

The wet desulphurisation and denitrification technique based on micro-nano bubbles, which is available by either D-method or I-method, is a promising novel process. By employing piped water, Na2SO3 aqueous solution and HA-Na aqueous solution as the absorption liquids, a comparative study was conducted in this article on D-method and I-method to analyze their performance, advantages and disadvantages. It was accompanied by an investigation of how initial pH and initial temperature values of the absorption liquids affected the removal efficiency. The results suggested a positive correlation between NO/SO2 removal efficiencies and pH values but a little improvement in the removal efficiency under alkaline conditions. Furthermore, heating the absorption liquids inhibited the removal of NO and SO2. When manipulated in the same experimental environment, D-method and I-method did not present a significant difference in the SO2 removal efficiency, while the former was remarkably more effective than the latter in removing NO. To put together, D-method had higher removal efficiency, but required a large-scale micro-nano bubble generator to process a large quantity of flue gas as the micro-nano bubble generator was subject to a limited inlet flow rate. Consequently, an increase in investment and operating costs was incurred, while this issue could be avoided by I-method.

16.
ACS Appl Mater Interfaces ; 14(30): 34918-34925, 2022 Aug 03.
Article in English | MEDLINE | ID: mdl-35868005

ABSTRACT

Perovskite light-emitting diodes (PeLEDs) show great potential in display and lighting because of their tunable wavelength, narrow emission bandwidths, and high color purity. Currently, the external quantum efficiency (EQE) of red and green PeLEDs has reached >23%. However, yellow PeLEDs are still rarely reported because of phase separation in mixed-halide perovskites and the coexistence of multiple phases in quasi-two-dimensional (quasi-2D) perovskites L2An-1BnX3n+1 (n = 1, 2, 3, ...), where L is a bulky organoammonium ligand. Here, we fabricate stable yellow PeLEDs by manipulating the phase distribution and incorporating rubidium cations (Rb+) in quasi-2D perovskites. The transient absorption results confirm that alkylammonium ligand butyl ammonium (BA) has a narrower phase distribution than phenylethyl ammonium (PEA) in the quasi-2D perovskites, resulting in a more blue-shifted emission peak. We further incorporate a proper molar ratio of Rb+ in the (BA)2CsPb2I7 perovskite to blue-shift the emission peak to the yellow range. Finally, the yellow PeLEDs exhibit an EQE of 3.5%, and the stable emission peak is located at 595 nm. Our work provides a useful approach for the fabrication of highly efficient and stable yellow PeLEDs.

17.
Adv Mater ; 34(35): e2203529, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35908154

ABSTRACT

Most methods of depositing perovskite films cannot meet the diverse requirements of real applications such as depositing films on various types of substrates, making patterns with different bandgaps for full-color display. Here, a robust mass transfer method of perovskite films and nanostructures is reported, meeting those requirements, by using an ultrathin branched polyethylenimine as interfacial chemical bonding layers. The transfer-printed perovskite films exhibit comparable morphology, composition, optoelectronic properties, and device performances with the counterparts made by optimized spin-coating methods. The perovskite light-emitting diodes (PeLEDs) using the transfer-printed films show decent external quantum efficiencies of 10.5% and 6.7% for red (680 nm) and sky-blue (493 nm) emissions, which are similar to the devices made by spin-coating. This robust transfer printing method also enables the the preparation of perovskite micropatterns with a high resolution up to 1270 pixels per inch. Horizontally aligned red and sky-blue perovskite microstripes are further obtained through multiple printing processes for white PeLEDs. This work demonstrates a feasible strategy for making perovskite films or micropatterns on various substrates for real applications in full-color display, white LEDs, lasing, etc.

18.
Cells ; 11(11)2022 06 04.
Article in English | MEDLINE | ID: mdl-35681539

ABSTRACT

Effective vaccination induces immune memory to protect animals upon pathogen re-encounter. Despite contradictory reports, bovine memory T cells are identified based on two isoforms of CD45, expression of CD45RO plus exclusion of CD45RA. In this report, we contrasted CD45RA/RO expression on circulatory T cells with IFNγ and IL4 expression induced by a conventional method. To our surprise, 20% of cattle from an enclosed herd did not express CD45RO on T cells without any significant difference on CD45RA expression and IFNγ or IL4 induction. In CD45RO expressing cattle, CD45RA and CD45RO expressions excluded each other, with dominant CD45RO (>90%) expression on gamma delta (γδ) followed by CD4+ (60%) but significantly higher CD45RA expression on CD8+ T cells (about 80%). Importantly, more than 80% of CD45RO expressing CD4+ and CD8+ T cells failed to produce IFNγ and IL-4; however, within the cytokine inducing cells, CD4+ T cells highly expressed CD45RO but those within CD8+ T cells mostly expressed CD45RA. Hence, CD45RO is not ubiquitously expressed in cattle, and rather than with memory phenotype, CD45RA/RO expression are more associated with distinct T cell subtypes.


Subject(s)
CD8-Positive T-Lymphocytes , Interleukin-4 , Animals , Cattle , Interferon-gamma , Lymphocyte Count , Phenotype
19.
J Phys Chem Lett ; : 5179-5185, 2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35658486

ABSTRACT

Incorporation of excess bulky organoammonium halides as additives is an efficient way to enhance the performance of perovskite light-emitting diodes (PeLEDs). The excess organoammonium halides can decrease the grain size and minimize the trap density to enhance radiative recombination. In this work, we reveal that the halides in excess additives also play a critical role in the operation stability of PeLEDs. With an increasing excess halide ratio, perovskite films gradually change from being rich in halide vacancies (VI) to being rich in halide interstitials (Ii), both of which can promote halide migration and reduce the operation stability. By using mixed 4-fluorophenylmethylammonium iodide and 4-fluorophenylmethylamine as additives, the excess halide ratio can be controlled and both VI and Ii can be minimized. Therefore, the operation stability of methylammonium lead iodide-based PeLEDs is enhanced significantly from 40 to 520 min. This work emphasizes the importance of controlling excess halide concentrations in terms of device performance and operation stability.

20.
Front Immunol ; 13: 779888, 2022.
Article in English | MEDLINE | ID: mdl-35371019

ABSTRACT

Cytotoxic T lymphocytes (CTLs) play an integral role in the adaptive immune response by killing infected cells. Antigen presenting cells (APCs), such as dendritic cells, present pathogenic peptides to the T cell receptor on the CTL surface and co-stimulatory signals required for complete activation. Activated CTLs secrete lytic granules containing enzymes that trigger target cell death at the CTL-target contact, also known as the immune synapse (IS). The actin and microtubule cytoskeletons are instrumental in the killing of CTL targets. Lytic granules are transported along microtubules to the IS, where granule secretion is facilitated by actin depletion and recovery. Furthermore, actomyosin contractility promotes target cell death by mediating mechanical force exertion at the IS. Recent studies have shown that inflammatory cytokines produced by APCs, such as interleukin-12 (IL-12), act as a third signal for CTL activation and enhance CTL proliferation and effector function. However, the biophysical mechanisms mediating such enhanced effector function remain unclear. We hypothesized that the third signal for CTL activation, IL-12, modulates cytoskeletal dynamics and force exertion at the IS, thus potentiating CTL effector function. Here, we used live cell total internal reflection fluorescence (TIRF) microscopy to study actomyosin and microtubule dynamics at the IS of murine primary CTLs activated in the presence of peptide-MHC and co-stimulation alone (two signals), or additionally with IL-12 (three signals). We found that three signal-activated CTLs have altered actin flows, myosin dynamics and microtubule growth rates as compared to two signal-activated CTLs. We further showed that lytic granules in three-signal activated CTLs are less clustered and have lower velocities than in two-signal activated CTLs. Finally, we used traction force microscopy to show that three signal-activated CTLs exert greater traction forces than two signal-activated CTLs. Our results demonstrate that activation of CTLs in the presence of IL-12 leads to differential modulation of the cytoskeleton, thereby augmenting the mechanical response of CTLs to their targets. This indicates a potential physical mechanism via which the third signal can enhance the CTL response.


Subject(s)
Antineoplastic Agents , T-Lymphocytes, Cytotoxic , Actin Cytoskeleton , Actins/metabolism , Actomyosin/metabolism , Animals , Interleukin-12/metabolism , Mice
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