Improved Homing of Antigen-Specific T Cells to Hodgkin’s Disease (HD) Tumor Cells by Forced Expression of CCR4 Receptor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 472-472
Author(s):  
A. Di Stasi ◽  
G. Dotti ◽  
A. Foster ◽  
L. Zhang ◽  
Helen H. Heslop ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Animal Studies ◽  
Cytotoxic T Cells ◽  
Antigen Specificity ◽  
Activated T Cells ◽  
Migration Assay ◽  
Cd8 Cells ◽  
Barr Virus

Abstract One crucial requirement for the success of any adoptive T cell transfer is that the effector T cells should migrate efficiently to the tumor site. Such an effect has been documented following adoptive transfer of Epstein-Barr virus specific cytotoxic T cells (EBV-CTLs). Antigenic stimulus from (normal and malignant) cells persistently infected with EBV led to expansion and sustained survival, and was also associated with activity against the EBV+ HD tumors. Since most HD patients have tumors that are EBV- but CD30+, we attempted to extend this approach by incorporating a CD30 chimeric receptor (CD30CAR) into the EBV-CTLs. Pre-clinical animal studies showed that CD30CAR+ EBV-CTLs readily migrated to EBV+/CD30+ tumors, but had limited capacity to localize to EBV−/CD30+ tumor cells. The likeliest explanation for this observation is that EBV- HD tumors produce the chemokine TARC, which attracts Th2 and regulatory T cells, but has little effect on EBV-CTLs, since these express low levels of the TARC receptor, CCR4. We hypothesized that forced expression of CCR4 by redirected EBV-CTLs would improve their homing to the EBV−/CD30+ HD cells. The full length of CCR4 receptor was cloned into the SFG retroviral vector and used to transduce both activated T cells and EBV-CTLs obtained from 6 and 4 healthy donors, respectively. Expression of CCR4 was 12±8% on activated T cells (mainly on CD4+ cells, 12±6%) and 4±5% on EBV-CTLs. After transduction with a CCR4, but not a control vector, expression of CCR4 increased to 53±24% (CD4+ 27±15% and CD8+ 17±9%) on activated T cells and 30±19% on EBV-CTLs. We then evaluated the capacity of control and transgenic T cells and EBV-CTLs to migrate in response to TARC, using a trans-well migration assay. Migration was tested against different CD30+ tumor lines producing TARC at low (Karpas wild type, <32 pg/ml) or high levels (Karpas engineered to produce TARC, HDLM-2 and L428, all TARC >2000pg/mL), measured by ELISA. The percent of cells migrating in the trans-well assay was significantly increased for CCR4 transgenic CD8+ selected T cells (54±11% with Karpas/TARC vs. 8±2% with media vs. 8±4% with Karpas-wt). Migration of control OKT3/28 blasts was less than 15% in all the conditions. Migration was significantly inhibited by the addition of antibody blocking TARC (<10%). An improved migration of CCR4+ CD8+ cells was observed also towards HDLM-2 (48±7%) and L428 (45±16%) as compared to control T cells (21±7% and 23±7%, respectively). Similarly, CCR4+ EBV-CTL showed improved migration towards Karpas/TARC (26±14%) as compared to Karpas/wt (12±8%) or media (10±7%). This genetic modification did not modify either the phenotype or the antigen specificity of EBV-CTLs, which retained the capacity to kill autologous EBV+ lymphoblastoid cells. We then determined if forced expression of CCR4 receptor was functional in vivo. To track homing of transgenic T cells, we transduced them with the FireFlyluciferase (FFLuc) vector and followed signal with a bioluminescent system (IVIS, Xenogen). Sublethally irradiated SCID mice were implanted s.c. with Karpas/wt on the left side and Karpas/TARC on the right side. When tumors were measurable, FFLuc+CCR4+ T cells were injected iv. By 24 hours post injection, signal was detectable only at the side of TARC secreting tumor cells, and signal persisted at 10 to 16 fold higher levels on the TARC+ side for >7 days. These data suggest that the migration of CARCD30 EBV-CTL to EBV−/CD30+ HD can be augmented by co-expressing the CCR4 receptor.

scholarly journals Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients

Blood ◽  
2009 ◽  
Vol 113 (11) ◽  
pp. 2442-2450 ◽  
Author(s):  
Chrystal U. Louis ◽  
Karin Straathof ◽  
Catherine M. Bollard ◽  
Claudia Gerken ◽  
M. Helen Huls ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Complete Response ◽  
Barr Virus ◽  
Significant Toxicity ◽  
Clinical Benefits ◽  
Epstein Barr

Treatment of Epstein-Barr virus (EBV)–positive nasopharyngeal carcinoma (NPC) with EBV-specific cytotoxic T cells (EBV-specific CTL) has been promising, producing clinical responses. However, infused EBV-specific CTL did not expand in vivo, likely limiting their antitumor activity. Lymphodepleting patients with chemotherapy before T-cell transfer enhances in vivo T-cell expansion, but results in nonspecific destruction of the resident immune system and can have significant toxicity. To evaluate if monoclonal antibodies (mAbs) can produce a more selective lymphodepletion, we conducted a clinical study in which NPC patients received a pair of lymphodepleting mAbs targeted to the CD45 antigen (CD45 mAbs) before EBV-specific CTL infusion. Eight patients with recurrent NPC received CD45 mAbs followed by escalating doses of auto-logous EBV-specific CTL. Infusion of CD45 mAbs resulted in transient lymphopenia in all patients and an increase in interleukin-15 (IL-15) levels in 6 out 8 patients. All patients had an increase in their peripheral blood frequency of EBV-specific T cells after CTL infusion. Three patients with a persistent increase had clinical benefits including 1 complete response (> 24 months) and 2 with stable disease (for 12 and 15 months). Lymphodepleting mAbs prior CTL transfer may represent an alternative to chemotherapy to enhance expansion of infused CTL. This study is registered at http://www.clinialtrials.gov as NCT00608257.

Mitomycin C-treated or irradiated concanavalin A-activated T cells augment the activation of cytotoxic T cells in vivo

1984 ◽  
Vol 88 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Cornelia Moyers ◽  
Christiane Pottmeyer-Gerber ◽  
Martin Gerber ◽  
Heinz Buszello ◽  
Wulf Dröge
Keyword(s):  
T Cells ◽  
Mitomycin C ◽  
Concanavalin A ◽  
Cytotoxic T Cells ◽  
Activated T Cells

Gene Transfer of IL-7R alpha (IL-7Rα) on Antigen-Specific Cytotoxic T Cells (CTLs) Restores Their Ability To Respond to IL-7 Cytokine.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2756-2756 ◽  
Author(s):  
J.F. Vera ◽  
V. Hoyos ◽  
B. Savoldo ◽  
C. Quintarelli ◽  
G. Giordano-Attianese ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Cells ◽  
Xenograft Model ◽  
Retroviral Vector ◽  
Effector Memory ◽  
Antigen Specificity ◽  
Clinical Value ◽  
Transgenic Expression ◽  
Mouse Xenograft Model

Abstract Systemic administration of IL-2 may improve the expansion and persistence of adoptively transferred anti-tumor CTLs. However, significant toxicity and concomitant expansion of regulatory T cells (Tregs) limit the clinical value of this strategy. IL-7 plays a crucial role in maintaining T-cell homeostasis, and administration appears well tolerated and not to expand Tregs. Nonetheless, the value of IL-7 for promoting proliferation of tumor-specific CTLs after adoptive transfer remains questionable, due to the lack of expression of the IL-7 receptor (IL-7Rα) on effector CTLs. Thus we have found IL-7Rα to be essentially undetectable in our model of EBV-specific CTL lines (EBV-CTLs) due to downregulation of IL-7Rα transcripts. To determine whether transgenic expression of IL-7Rα can restore the capacity of established EBV-CTLs to respond to IL-7, the full-length of IL-7Rα was cloned in the SFG retroviral vector (SFG/IL-7Rα). We transduced EBV-CTLs generated from 5 healthy donors and evaluated their growth kinetics and antigen specificity. As control, EBV-CTLs were transduced with the SFG retroviral vector encoding for a truncated form of the CD34 molecule (SFG.ΔCD34). After transduction with SFG/IL-7Rα, IL-7Rα was detectable in 58% to 76% of EBV-CTLs. The transgenic IL-7Rα was functional since addition of IL-7 (2ng/mL) to transgenic cells induced phosphorylation of STAT5 within 10 min. To evaluate whether rhIL-7 sustained the expansion of EBV-CTLs/IL-7Rα+, transduced CTLs were stimulated weekly with autologous EBV-LCLs in the presence of IL-2 (50U/mL) or IL-7 (2ng/mL). Control EBV-CTLs and EBV-CTLs/IL-7Rα+ expanded equally well with IL-2. However, only EBV-CTL/IL-7Rα+ significantly proliferated in the presence of IL-7 [from 1×106 cells to 103×106 cells (range, 38-286×106)] over a period of five weeks. CTL expansion remained antigen dependent, and antigen withdrawal led to cessation of CTL growth. EBV-CTLs/IL-7Rα+ showed the expected growth advantage in the presence of IL-7, increasing from 55%±15% to 79%±5% of the total within 5 weeks. In contrast, the proportion of IL-7Rα+ cells marginally declined when the cells were expanded with IL-2 (from 64%±14% to 40%±11%). Importantly, EBV-CTLs/IL7Rα+ expanded with IL-7 retained their ability to respond to other common-γ-chain cytokines. EBV-CTLs/IL7Rα+ grown with IL-7 for more than 2 weeks, expanded further when exposed to both antigen and IL-2 or IL-15. Control CTLs grown with IL-2 and EBV-CTLs/IL-7Rα+ grown with IL-7 both remained polyclonal, as assessed by VβTCR repertoire analysis, and were mostly CD3+/CD8+ (> 90±8%) with an effector-memory profile. EBV-CTLs/IL-7Rα+ also retained antigen specificity measured by tetramer staining, by IFNγ release in response to EBV-peptides and by MHC-restricted killing of autologous LCLs (52%±18% at a ratio 20:1 vs 9±17% of allogeneic LCL); this killing was comparable to the activity of control CTLs cultured in IL-2 (51%±27%). Preliminary studies indicate that EBV-CTLs/IL-7Rα+ also expand in vivo in response to IL-7 and maintain their anti-tumor activity in a SCID mouse xenograft model.

scholarly journals Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells.

1990 ◽  
Vol 172 (4) ◽  
pp. 1083-1090 ◽  
Author(s):  
A Aggarwal ◽  
S Kumar ◽  
R Jaffe ◽  
D Hone ◽  
M Gross ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Cells ◽  
Oral Immunization ◽  
Full Length ◽  
Class I ◽  
Peptide Epitope ◽  
Cd8 Cells ◽  
Flanking Sequences

Oral immunization with an attenuated Salmonella typhimurium recombinant containing the full-length Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I-restricted CD8+ cytotoxic T cells that are directed against the P. berghei CS peptide epitope spanning amino acids 242-253. This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. falciparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences. Both of these vaccines were able to induce CD8+ CTL directed against P. falciparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8+ CTL in immunity to malaria.

scholarly journals Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+,2- T cells. Tumor eradication does not require participation of cytotoxic T cells.

1985 ◽  
Vol 161 (5) ◽  
pp. 1122-1134 ◽  
Author(s):  
P D Greenberg ◽  
D E Kern ◽  
M A Cheever
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Disseminated Tumor Cells ◽  
Delayed Type Hypersensitivity ◽  
Cell Compartment ◽  
Histocompatibility Complex ◽  
Tumor Eradication

The ability of noncytolytic Lyt-1+,2- T cells immune to FBL-3 leukemia to effect eradication of disseminated FBL-3 was studied. Adult thymectomized, irradiated, and T-depleted bone marrow-reconstituted (ATXBM) B6 hosts were cured of disseminated FBL-3 by treatment with 180 mg/kg cyclophosphamide (CY) and adoptively transferred Lyt-1+,2- T cells obtained from congenic B6/Thy-1.1 donors immune to FBL-3. Analysis of the T cell compartment of ATXBM hosts treated and rendered tumor-free by this therapy revealed that the only T cells present in the mice were donor-derived Lyt-1+,2- T cells. In vitro stimulation of these T cells with FBL-3 tumor cells, which express class I but no class II major histocompatibility complex antigens, induced lymphokine secretion, but did not result in the generation of cytotoxic T lymphocytes (CTL). Thus, in a setting in which mice lack Lyt-2+ T cells, and in which no CTL of either host or donor origin could be detected, immune Lyt-1+,2- T cells, in conjunction with CY, mediated eradication of a disseminated leukemia. The results suggest that delayed-type hypersensitivity responses induced by immune T cells represent a potentially useful effector mechanism for in vivo elimination of disseminated tumor cells.

Epstein Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes (CTL) Expressing an Anti-CD30 Chimeric T Cell Receptor (CTCR) for the Treatment of Hodgkin’s Disease (HD).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 745-745
Author(s):  
B. Savoldo ◽  
C. M. Rooney ◽  
H. E. Heslop ◽  
H. Abken ◽  
A. Hombach ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Cell Lines ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Barr Virus

Abstract HD may be a suitable target for immunotherapy, and in patients with EBV-associated HD, adoptive transfer of EBV-CTL has produced disease responses. An alternative target is the CD30 molecule, which is present on the malignant cells of almost all patients with HD. CD30 is a member of the TNF superfamily and monoclonal antibodies directed to this antigen are currently under investigation in patients with relapsed HD. An alternative way to target CD30 is by the construction of T cells expressing cTcR specific for the antigen. T lymphocytes engineered to express this cTcR can specifically kill CD30+ HD cell lines {Cancer Res,1998;58:1116}. However, these chimeric molecules connect the antigen-recognition properties of CD30 antibodies with the endodomain of CD3ζ, which is insufficient to fully activate resting T cells to proliferate and release cytokines. As a consequence chimeric T cells that express these endodomains divide infrequently, lose activity and have performed poorly in-vivo. Full T cell activation requires receptor engagement to be accompanied by a sequence of co-stimulatory stimuli. We have shown that EBV-CTL can fulfill this need, since the co-stimulatory signals delivered by EBV-infected B cells after native receptor engagement ensure full functionality when the CTL subsequently bind to tumor cells through their cTcR. We first evaluated whether EBV-CTL can be redirected to kill CD30+ HD cell lines and whether they retain their specificity and antigen repertoire. EBV-CTLs were prepared from 8 EBV+ healthy donors using weekly stimulation with irradiated autologous EBV-transformed lymphoblastoid cell lines (LCL) in the presence of IL-2 (50U/mL). CTL were transduced after the 3rd stimulation and further expanded with 3–4 weekly LCL/IL-2 stimulations. The expansion rate of the transduced CTL was similar to that of control EBV-CTL. Transduced CTL retained killing of their autologous LCL targets through their native receptor (64.4±16% at 20:1 E:T ratio), and became able to lyse CD30+ malignant lymphoma targets through their cTcR (e.g. HDLM-2=45.4±16% and Karpas-299=42.5±17%). Killing of CD30+ tumor cells was significantly inhibited by preincubation with an anti-CD30 blocking antibody (16.5±12%). Of potential concern, however, is that CD30 is expressed by activated normal T lymphocytes: expression was undetectable on resting T cells, but increased to 3–32% on day 4–7 after stimulation with LCL. Fortunately, expression dwindles to 3–6% by two weeks as an EBV-specific line emerges, suggesting that CD30 is expressed only in the early phases of T cell activation. As anticipated from these data, therefore, expression of a CD30 cTcR did not impair the antigenic repertoire of the EBV-CTL, which retained the same pattern of immunodominant MHC class I epitopes (detected by tetramer) as control cells. We also performed co-culture experiments to evaluate whether infusion of CTL-CD30 cTcR could cross-compromise the primary reactivation of other virus-specific CTL. Autologous EBV-CTLs engineered to express the CD30-cTcR were added to cultures of PBMC stimulated to reactivate cytomegalovirus- or adenovirus-specific CTL. In 4/4 donors, the percentage of CMV pp65+ T cells did not change, while generation of adenovirus-specific T cells (Hexon-tetramer+) was significantly reduced in only 1/3 donor. These data support the feasibility of using EBV-CTL bearing a cTcR for CD30 to treat both EBV+ and EBV− HD.

scholarly journals Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3865-3870 ◽  
Author(s):  
Katja Mauerer Zirlik ◽  
David Zahrieh ◽  
Donna Neuberg ◽  
John G. Gribben
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Binding Affinity ◽  
Primary Tumor ◽  
Cytotoxic T Cells ◽  
Lymphocytic Leukemia ◽  
Limiting Factor ◽  
Native Peptide ◽  
Heteroclitic Peptides

AbstractHeteroclitic peptide modifications increase immunogenicity, allowing generation of cytotoxic T lymphocytes (CTLs) against weakly immunogenic tumor-associated antigens (TAAs). A critical issue is whether T cells generated against heteroclitic peptides retain the ability to recognize and kill tumor cells expressing the original weak TAAs, and whether there is a lower threshold of binding affinity of the native peptides, below which such CTLs can still kill primary tumor cells. To examine this we used a model examining the ability of native and heteroclitic immunoglobulin (Ig)–derived peptides to generate CTLs that can kill chronic lymphocytic leukemia (CLL) cells. We demonstrate that CTLs generated against heteroclitic peptides have enhanced killing of CD40-activated B cells pulsed with either heteroclitic (P < .001) or native peptide (P = .04) and primary CLL cells (P = .01). The novel finding reported here is that the rate-limiting factor appears to be the ability to generate CTLs and that once generated, CTL lysis of primary tumor cells is independent of the binding affinity of the native peptide. These findings have implications for vaccination strategies in malignancies and are currently being further examined in vivo in murine models.

scholarly journals Partial absence of PD-1 expression by tumor-specific CD8+ T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report

2019 ◽  
Author(s):  
Yannick Simoni ◽  
Etienne Becht ◽  
Shamin Li ◽  
Chiew Yee Loh ◽  
Joe Poh Sheng Yeong ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Lung Tumor ◽  
Tumor Infiltrating Lymphocytes ◽  
Antigen Specificity ◽  
Barr Virus ◽  
Ebv Infection ◽  
Asian Populations ◽  
Epstein Barr ◽  
Two Populations

AbstractLymphoepithelioma-like carcinoma (LELC) is an uncommon lung cancer, typically observed in young, non-smoking Asian populations. LELC is associated with Epstein-Barr virus (EBV) infection of lung tumor cells of epithelial origin, suggesting a carcinogenic role of EBV as observed in nasopharyngeal carcinoma (NPC). Here, we studied the antigen specificity and phenotype of CD8+ tumor infiltrating lymphocytes (TILs) in one LELC patient positive for EBV infection in lung tumor cells. Using MHC class I tetramers, we detected two populations of EBV-specific CD8+ TILs, which can be considered as tumor-specific CD8+ T cells, in the tumor of this patient. Transcriptomic analyses of these two populations reveal their distinct exhausted profiles and polyclonal TCR repertoire. High dimensional analyses at single cell level using mass cytometry showed showed that populations of tumor specific CD8+ TILs are phenotypically heterogeneous, although they consistently express CD39. Unexpectedly, although the LELC tumor cells expressed abundant PD-L1, these tumor-specific CD8+ TILs mostly did not express PD-1, suggesting that anti-PD1/PD-L1 immunotherapy may not be an appropriate strategy for disinhibiting EBV-specific cells for the treatment of LELC patients. These results might also help to explain low rates of checkpoint blockade immunotherapy response for NPC, despite the antigenicity of EBV for both tumor types.

P–398 Decidualization inhibits the expression of CXCR3-binding chemokines by human decidual stromal cells. Role in maternal-fetal immune tolerance

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Llorca ◽  
O García ◽  
R Martínez ◽  
C Méndez ◽  
M J Ruiz ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Tolerance ◽  
Stromal Cells ◽  
First Trimester ◽  
Peripheral Blood Lymphocytes ◽  
Conditioned Media ◽  
Activated T Cells ◽  
Migration Assay

Abstract Study question We aimed to analyze the effects of decidualization on the expression of chemokines that attract abortogenic T cells by human DSCs. Summary answer Decidualization inhibits the expression of chemokines that attract Th1 and Tc1 cells by DSCs, thereby preventing the arrival of abortogenic T cells into the decidua. What is known already Decidual stromal cells (DSCs) are the most abundant cells in the human decidua, the tissue that constitutes the maternal component of the placenta. Numerous evidences confirm that DSCs play a key role in maternal-fetal immune tolerance. In normal pregnancy, DSCs undergo a process of differentiation (decidualization) under the effect of progesterone and other pregnancy hormones. Decidualized DSCs become rounded and secrete prolactin, IL–15 and other factors. In the mouse, it has been observed that during pregnancy, DSCs inhibit the expression of chemokines that attract abortogenic Th1 and Tc1 cells from blood to the decidua. Study design, size, duration We compared the expression of CXCR3-binding chemokines by undifferentiated and decidualized human DSCs. We also compared the capacity of these cells to attract activated Th1 and Tc1 cells in vitro. Ten DSC lines were obtained from elective vaginal terminations of first-trimester pregnancies (6–11 weeks). Donors were healthy women aged 20–30 years. Informed consent was obtained from each donor. This study was approved by the Research and Ethics Committee of the University of Granada. Participants/materials, setting, methods Decidual stromal cell lines were established as previously described. These lines were decidualized with progesterone and cAMP in vitro. The expression of chemokines by these cells was studied by RT-PCR. Peripheral blood lymphocytes were activated with PHA, anti-CD28 and IL–2. As a consequence of this activation, CXCR3+ Th1 and Tc1 cells were produced. We used a migration assay in Transwell chambers to study the capacity of DSCs to attract these activated T cells. Main results and the role of chance We observed that those chemokines that bind to CXCR3, a chemokine receptor detected in activated Th1 and Tc1 cells, were not expressed by either undifferentiated and decidualized DSCs (CXCL9) or their expression was inhibited in decidualized DSCs (CXCL10 P &lt; 0.01, CXCL11 P &lt; 0.05). We found that conditioned media of undifferentiated DSCs decreased the migration of CXCR3+ activated T cells (Th1 and Tc1 cells) (P &lt; 0.05), and this effect was even stronger with conditioned media of decidialized DSCs P &lt; 0.001). These results demonstrated that decidualization of DSCs during pregnancy inhibits the expression of chemokines that attract Th1 and Tc1 cells by DSCs, thereby preventing the arrival of abortogenic T cells into the decidua. Limitations, reasons for caution This is an in vitro study due to the impossibility of performing an in vivo study in humans for ethical reasons. Wider implications of the findings: Several publications have shown that DSCs have a therapeutic effect in various Th1-associated diseases. Our results explain this effect and suggest the extension of the use of these cells in the treatment of this type of diseases. Trial registration number Not applicable

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