scholarly journals Vγ9Vδ2 T cells as a promising innovative tool for immunotherapy of hematologic malignancies

2011 ◽  
Vol 4 (4) ◽  
pp. 211
Author(s):  
Serena Meraviglia ◽  
Carmela La Mendola ◽  
Valentina Orlando ◽  
Francesco Scarpa ◽  
Giuseppe Cicero ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Hematologic Malignancies ◽  
Cytolytic Activity ◽  
Cell Therapies ◽  
Stressed Cells

The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of the direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen- or aminobisphosphonate-activated Vγ9Vδ2 T lymphocytes in humans. In this review, we focus on the recent advances in the activation/expansion of γδ T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with hematologic malignancies.<br />

TCR and DNAM Dependent Lysis of Acute Monocytic Leukemia (AMoL) by Vg9Vd2 T Lymphocytes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1041-1041
Author(s):  
Julie Gertner-Dardenne ◽  
Eloise Perrot ◽  
Thomas Prebet ◽  
Aude Charbonnier ◽  
Helene Sicard ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
T Lymphocytes ◽  
Myeloid Leukemia ◽  
Ex Vivo ◽  
Acute Myeloid

Abstract Abstract 1041 Poster Board I-63 BACKGROUNd: Compelling evidences have demonstrated the role of the immune system in the control of acute myeloid leukemia (AML). So far, T cells and natural killer (NK) cells are the major immune effectors shown to be involved in AML control. The graft-versus-leukemia (GVL) effect following allogenic stem cell transplantation as well as donor lymphocyte infusions indicate that T lymphocytes can control and eliminate AML cells. Leukemia-specific antigenic peptides have been characterized (proteinase-3 and Wilms tumor 1 protein) and serve as targets for peptide-based vaccine trials in AML. Allogenic NK cells have anti-leukemic activity as shown by killer cell inhibitory receptor (KIR)-mismatched haplo-identical stem cell transplantation. Less is known regarding the role of gd T cells in the control of AML. Recently the reconstitution of Vd1 T lymphocytes post transplantation has been shown to correlate with a better prognosis. In the present study, we have analyzed gd T cells in patients with AML and in a mouse model of human AML and focused on (Vg9) Vd2 T cells, the main subset of circulating gd T cells with anti-neoplastic activity. Human Vg9Vd2 T lymphocytes can be activated by nonpeptidic antigens such as the mevalonate pathway-derived isopentenyl pyrophosphate or synthetic phosphoantigen such as bromohydrin pyrophosphate (BrHPP). This population may be suitable for the adoptive immunotherapy of acute myeloid leukemia (AML). However little is known about the frequency, the function and the mechanisms underlying Vg9Vd2 T-cell recognition of AML. We have focused this study on AMoL which are targets of NK and ab T cells. OBJECTIVE OF THE STUDY to describe Vg9Vd2 T cells in patients with AML and investigate their ability to induce an effective cytotoxic response against autologous AML blast in vitro and in vivo. EXPERIMENTAL PROCEDURe: We compared the phenotype and the absolute circulating Vg9Vd2 T cell levels in the blood and the bone marrow (BM) in 12 patients with AMoL (FAB AML-M4 and -M5) and 12 healthy volunteers (HV) using multi parametric flow cytometry. All patients and volunteers gave written informed consent. Vg9Vd2 T cells of AML patient were expanded ex vivo using BrHPP or Zoledronic acid plus IL2. The functions of expanded Vg9Vd2 T cells were assessed in vitro by their cytotoxicity against leukemic blasts (CD107a staining, 51Cr assay) and in vivo in immunodeficient mice transplanted with human AML cell line (U937). In these experiments, the ability of adoptively transferred Vg9Vd2 T cells to migrate into BM and improve mice survival was assessed after i.v. infusion of U937 cells into healthy female NOD-SCID, common _-chain knockout mice (NOG mice). Mice were then treated twice i.v. with 40.106 Vg9Vd2 T cells. RESULTs: Vg9Vd2 T lymphocytes are present in the blood as well as BM of AMoL patients at a lower frequency as compared to HV (median 2.07/μl vs 34/μL respectively P<0.001). Vg9Vd2 T lymphocytes from AML patients are endowed with in vitro proliferation in response to BrHPP or Zoledronic acid plus IL2 but lower than HV (fold increase median 33 versus 69, P=0.051). Expanded Vg9Vd2 express activation markers (CD69 and CCR5) and exhibit an effector/memory phenotype (CD45RA- CD27-). Their lytic potential toward autologous AML blast was equivalent to those of HV by 51Cr experiments and CD107a staining and involves the perforin-granzyme pathway. Their activity depends on both TCRVd2 and DNAX accessory molecule-1 (DNAM-1) as demonstrated by antibody blockade. In vivo data show that, upon sacrifice, Vg9Vd2 were detected in BM, spleen and blood of mice. Preliminary Kaplan-Meier analysis of pooled cohorts of Vg9Vd2-treated and untreated mice reveals that mice receiving Vg9Vd2 T cells displayed superior survival compared with untreated controls (P=0.0047). CONCLUSIOn: Altogether, our data indicate that Vg9Vd2 T cells are decreased in AML patients and have a more limited expansion potential. However, they are able to kill autologous AML blast upon stimulation in a TCRVd2 as well as the DNAM-1 receptor dependent manner. These results provide a rationale for the clinical evaluation of adoptive transfer of ex vivo expanded allogenic Vg9Vd2T cells or direct activation of Vg9Vd2T cells with IL2 + phosphoantigens in patients with AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Neo-Antigen mRNA Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 776
Author(s):  
Arthur Esprit ◽  
Wout de Mey ◽  
Rajendra Bahadur Shahi ◽  
Kris Thielemans ◽  
Lorenzo Franceschini ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Vaccines ◽  
Ex Vivo ◽  
Cell Activity ◽  
Cell Therapies ◽  
Central Tolerance ◽  
Cell Genome ◽  
Therapeutic Cancer Vaccines

The interest in therapeutic cancer vaccines has caught enormous attention in recent years due to several breakthroughs in cancer research, among which the finding that successful checkpoint blockade treatments reinvigorate neo-antigen-specific T cells and that successful adoptive cell therapies are directed towards neo-antigens. Neo-antigens are cancer-specific antigens, which develop from somatic mutations in the cancer cell genome that can be highly immunogenic and are not subjected to central tolerance. As the majority of neo-antigens are unique to each patient’s cancer, a vaccine technology that is flexible and potent is required to develop personalized neo-antigen vaccines. In vitro transcribed mRNA is such a technology platform and has been evaluated for delivery of neo-antigens to professional antigen-presenting cells both ex vivo and in vivo. In addition, strategies that support the activity of T cells in the tumor microenvironment have been developed. These represent a unique opportunity to ensure durable T cell activity upon vaccination. Here, we comprehensively review recent progress in mRNA-based neo-antigen vaccines, summarizing critical milestones that made it possible to bring the promise of therapeutic cancer vaccines within reach.

scholarly journals Lingering effects of chemotherapy on mature T cells impair proliferation

2020 ◽  
Vol 4 (19) ◽  
pp. 4653-4664
Author(s):  
Rajat K. Das ◽  
Roddy S. O’Connor ◽  
Stephan A. Grupp ◽  
David M. Barrett
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
Hematologic Malignancies ◽  
Cell Therapies ◽  
Pediatric Cancer Patients ◽  
Clinical Responses ◽  
Manufacturing Techniques

Abstract Engineered T-cell therapies have demonstrated impressive clinical responses in patients with hematologic malignancies. Despite this efficacy, many patients have a transient persistence of T cells, which can be correlated with transient clinical response. Translational data on T cells from pediatric cancer patients shows a progressive decline in chimeric antigen receptor (CAR) suitability with cumulative chemotherapy regardless of regimen. We investigated the effects of chemotherapy on surviving T cells in vitro, describing residual deficits unique to each agent including mitochondrial damage and metabolic alterations. In the case of cyclophosphamide but not doxorubicin or cytarabine, these effects could be reversed with N-acetylcysteine. Specifically, we observed that surviving T cells could be stimulated, expanded, and transduced with CARs with preserved short-term cytolytic function but at far lower numbers and with residual metabolic deficits. These data have implications for understanding the effects of chemotherapy on mature T cells later collected for adoptive cell therapy, as chemotherapy-exposed T cells may have lingering dysfunction that affects ex vivo adoptive cell therapy manufacturing techniques and, ultimately, clinical efficacy.

scholarly journals Effect of ex vivo-expanded γδ-T cells combined with galectin-1 antibody on the growth of human cervical cancer xenografts in SCID mice

2010 ◽  
Vol 33 (5) ◽  
pp. 280 ◽  
Author(s):  
Hua Li ◽  
Yubin Wang ◽  
FuXiang Zhou
Keyword(s):  
Cervical Cancer ◽  
T Cells ◽  
Antitumor Activity ◽  
Western Blot ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Antibody Treatment ◽  
Human Cervical Cancer

Objective: To investigate the antitumor activity of ex vivo-expanded γδ-T cells derived from tumor-infiltrating lymphocytes(γδTILs) from cervical cancer patients when combined with galectin-1 antibody and studied both in vitro and in vivo. Methods: The presence of γδTILs in cervical cancer specimens was detected by immunohistochemistry and γδTILs were expanded using the solid-phase antibody method. The expression of galectin-1 by the human cervical cancer cell line, SiHa, was measured by Western blot and ELISA. In vitro cytotoxic activities of expanded γδTILs, with or without galectin-1 inhibitor, were determined using the LDH-release test. In vivo antitumor activity of γδTILs, combined with galectin-1 antibody, was evaluated using the SCID mouse model. Results: γδTILs existed in the cervical cancer and the percentage of TCRγδ+ cells in γδTILs after ex vivo expansion was 91.2±1.2% detected by flow cytometry. SiHa cell expressed and secreted galectin-1 as measured by Western blot and ELISA. Expanded γδTILs from human cervical cancer demonstrated marked cytotoxicity to SiHa or Hela cells. In comparison with non-treated group, the cytotoxicity of γδ TILs towards SiHa or Hela cell was significantly increased when effector and target cells were incubated with either lactose or galectin-1 antibody at E/T ratio of 1:1 (p < 0.05). γδTILs, in combination with galectin-1 antibody treatment, significantly suppressed the growth of xenografts in SCID mice, in comparison with all other groups (p < 0.05). γδTILs alone also showed the ability to inhibit tumour growth in vivo, but were more efficient when combined with specific antibody (p < 0.05). Conclusion: Taken together, our results suggest that γδ-T cells, combined with galectin-1 antibody treatment, could be a more effective adoptive immunotherapy for patients with cervical cancer than traditional adoptive immunotherapy methods.

scholarly journals Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David S. Fischer ◽  
Meshal Ansari ◽  
Karolin I. Wagner ◽  
Sebastian Jarosch ◽  
Yiqi Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Ex Vivo ◽  
Severe Disease ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Single Cell Rna Sequencing

AbstractThe in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induce transcriptional shifts by antigenic stimulation in vitro and take advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for ‘reverse phenotyping’. This allows identification of SARS-CoV-2-reactive TCRs and reveals phenotypic effects introduced by antigen-specific stimulation. We characterize transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and show correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.

98 ATA3271: an armored, next-generation off-the-shelf, allogeneic, mesothelin-CAR T cell therapy for solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A109-A109
Author(s):  
Jiangyue Liu ◽  
Xianhui Chen ◽  
Jason Karlen ◽  
Alfonso Brito ◽  
Tiffany Jheng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Next Generation ◽  
Phase 3 ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cells ◽  
Car T

BackgroundMesothelin (MSLN) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein with high expression levels in an array of malignancies including mesothelioma, ovaria, non-small cell lung cancer, and pancreatic cancers and is an attractive target antigen for immune-based therapies. Early clinical evaluation of autologous MSLN-targeted chimeric antigen receptor (CAR)-T cell therapies for malignant pleural mesothelioma has shown promising acceptable safety1 and have recently evolved with incorporation of next-generation CAR co-stimulatory domains and armoring with intrinsic checkpoint inhibition via expression of a PD-1 dominant negative receptor (PD1DNR).2 Despite the promise that MSLN CAR-T therapies hold, manufacturing and commercial challenges using an autologous approach may prove difficult for widespread application. EBV T cells represent a unique, non-gene edited approach toward an off-the-shelf, allogeneic T cell platform. EBV-specific T cells are currently being evaluated in phase 3 trials [NCT03394365] and, to-date, have demonstrated a favorable safety profile including limited risks for GvHD and cytokine release syndrome.3 4 Clinical proof-of-principle studies for CAR transduced allogeneic EBV T cell therapies have also been associated with acceptable safety and durable response in association with CD19 targeting.5 Here we describe the first preclinical evaluation of ATA3271, a next-generation allogeneic CAR EBV T cell therapy targeting MSLN and incorporating PD1DNR, designed for the treatment of solid tumor indications.MethodsWe generated allogeneic MSLN CAR+ EBV T cells (ATA3271) using retroviral transduction of EBV T cells. ATA3271 includes a novel 1XX CAR signaling domain, previously associated with improved signaling and decreased CAR-mediated exhaustion. It is also armored with PD1DNR to provide intrinsic checkpoint blockade and is designed to retain functional persistence.ResultsIn this study, we characterized ATA3271 both in vitro and in vivo. ATA3271 show stable and proportional CAR and PD1DNR expression. Functional studies show potent antitumor activity of ATA3271 against MSLN-expressing cell lines, including PD-L1-high expressors. In an orthotopic mouse model of pleural mesothelioma, ATA3271 demonstrates potent antitumor activity and significant survival benefit (100% survival exceeding 50 days vs. 25 day median for control), without evident toxicities. ATA3271 maintains persistence and retains central memory phenotype in vivo through end-of-study. Additionally, ATA3271 retains endogenous EBV TCR function and reduced allotoxicity in the context of HLA mismatched targets. ConclusionsOverall, ATA3271 shows potent anti-tumor activity without evidence of allotoxicity, both in vitro and in vivo, suggesting that allogeneic MSLN-CAR-engineered EBV T cells are a promising approach for the treatment of MSLN-positive cancers and warrant further clinical investigation.ReferencesAdusumilli PS, Zauderer MG, Rusch VW, et al. Abstract CT036: A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy. Cancer Research 2019;79:CT036-CT036.Kiesgen S, Linot C, Quach HT, et al. Abstract LB-378: Regional delivery of clinical-grade mesothelin-targeted CAR T cells with cell-intrinsic PD-1 checkpoint blockade: Translation to a phase I trial. Cancer Research 2020;80:LB-378-LB-378.Prockop S, Doubrovina E, Suser S, et al. Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation. J Clin Invest 2020;130:733–747.Prockop S, Hiremath M, Ye W, et al. A Multicenter, Open Label, Phase 3 Study of Tabelecleucel for Solid Organ Transplant Subjects with Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease (EBV+PTLD) after Failure of Rituximab or Rituximab and Chemotherapy. Blood 2019; 134: 5326–5326.Curran KJ, Sauter CS, Kernan NA, et al. Durable remission following ‘Off-the-Shelf’ chimeric antigen receptor (CAR) T-Cells in patients with relapse/refractory (R/R) B-Cell malignancies. Biology of Blood and Marrow Transplantation 2020;26:S89.

scholarly journals IMMU-31. QUANTITATIVE EVALUATION OF ROUTES OF ADMINISTRATION OF IMMUNOTHERAPEUTIC T CELLS TO ORTHOTOPIC GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii111-ii111
Author(s):  
Lan Hoang-Minh ◽  
Angelie Rivera-Rodriguez ◽  
Fernanda Pohl-Guimarães ◽  
Seth Currlin ◽  
Christina Von Roemeling ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
Adoptive T Cell Therapy ◽  
Whole Body ◽  
T Cell Therapy ◽  
Clinical Responses

Abstract SIGNIFICANCE Adoptive T cell therapy (ACT) has emerged as the most effective treatment against advanced malignant melanoma, eliciting remarkable objective clinical responses in up to 75% of patients with refractory metastatic disease, including within the central nervous system. Immunologic surrogate endpoints correlating with treatment outcome have been identified in these patients, with clinical responses being dependent on the migration of transferred T cells to sites of tumor growth. OBJECTIVE We investigated the biodistribution of intravenously or intraventricularly administered T cells in a murine model of glioblastoma at whole body, organ, and cellular levels. METHODS gp100-specific T cells were isolated from the spleens of pmel DsRed transgenic C57BL/6 mice and injected intravenously or intraventricularly, after in vitro expansion and activation, in murine KR158B-Luc-gp100 glioma-bearing mice. To determine transferred T cell spatial distribution, the brain, lymph nodes, heart, lungs, spleen, liver, and kidneys of mice were processed for 3D imaging using light-sheet and multiphoton imaging. ACT T cell quantification in various organs was performed ex vivo using flow cytometry, 2D optical imaging (IVIS), and magnetic particle imaging (MPI) after ferucarbotran nanoparticle transfection of T cells. T cell biodistribution was also assessed in vivo using MPI. RESULTS Following T cell intravenous injection, the spleen, liver, and lungs accounted for more than 90% of transferred T cells; the proportion of DsRed T cells in the brains was found to be very low, hovering below 1%. In contrast, most ACT T cells persisted in the tumor-bearing brains following intraventricular injections. ACT T cells mostly concentrated at the periphery of tumor masses and in proximity to blood vessels. CONCLUSIONS The success of ACT immunotherapy for brain tumors requires optimization of delivery route, dosing regimen, and enhancement of tumor-specific lymphocyte trafficking and effector functions to achieve maximal penetration and persistence at sites of invasive tumor growth.

γδ T cells for immune therapy of patients with lymphoid malignancies

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 200-206 ◽  
Author(s):  
Martin Wilhelm ◽  
Volker Kunzmann ◽  
Susanne Eckstein ◽  
Peter Reimer ◽  
Florian Weissinger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Low Dose ◽  
Γδ T Cells ◽  
Low Grade ◽  
Treatment Schedule ◽  
Γδ T Cell

Abstract There is increasing evidence that γδ T cells have potent innate antitumor activity. We described previously that synthetic aminobisphosphonates are potent γδ T cell stimulatory compounds that induce cytokine secretion (ie, interferon γ [IFN-γ]) and cell-mediated cytotoxicity against lymphoma and myeloma cell lines in vitro. To evaluate the antitumor activity of γδ T cells in vivo, we initiated a pilot study of low-dose interleukin 2 (IL-2) in combination with pamidronate in 19 patients with relapsed/refractory low-grade non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). The objectives of this trial were to determine toxicity, the most effective dose for in vivo activation/proliferation of γδ T cells, and antilymphoma efficacy of the combination of pamidronate and IL-2. The first 10 patients (cohort A) who entered the study received 90 mg pamidronate intravenously on day 1 followed by increasing dose levels of continuous 24-hour intravenous (IV) infusions of IL-2 (0.25 to 3 × 106 IU/m2) from day 3 to day 8. Even at the highest IL-2 dose level in vivo, γδ T-cell activation/proliferation and response to treatment were disappointing with only 1 patient achieving stable disease. Therefore, the next 9 patients were selected by positive in vitro proliferation of γδ T cells in response to pamidronate/IL-2 and received a modified treatment schedule (6-hour bolus IV IL-2 infusions from day 1-6). In this patient group (cohort B), significant in vivo activation/proliferation of γδ T cells was observed in 5 patients (55%), and objective responses (PR) were achieved in 3 patients (33%). Only patients with significant in vivo proliferation of γδ T cells responded to treatment, indicating that γδ T cells might contribute to this antilymphoma effect. Overall, administration of pamidronate and low-dose IL-2 was well tolerated. In conclusion, this clinical trial demonstrates, for the first time, that γδ T-cell–mediated immunotherapy is feasible and can induce objective tumor responses. (Blood. 2003;102:200-206)

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

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