scholarly journals Increased Expression of Ganglioside GM1 in Peripheral CD4+ T Cells Correlates Soluble Form of CD30 in Systemic Lupus Erythematosus Patients

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Lingli Dong ◽  
Shaoxian Hu ◽  
Fang Chen ◽  
Xiaomei Lei ◽  
Wei Tu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Elevated Serum ◽  
Soluble Form ◽  
Membrane Microdomains ◽  
Tnf Alpha ◽  
Healthy Controls ◽  
Soluble Cd30

Gangliosides GM1 is a good marker of membrane microdomains (lipid rafts) with important function in cellular activation processes. In this study we found that GM1 expression on CD4+ T cells and memory T cells (CD45RO/CD4) were dramatic increased after stimulation with phytohaemagglutinin in vitro. Next, we examined the GM1 expression on peripheral blood CD4+ T cells and CD8+ T cells from 44 patients with SLE and 28 healthy controls by flow cytometry. GM1 expression was further analyzed with serum soluble CD30 (sCD30), IL-10, TNF-alpha and clinical parameters. The mean fluorescence intensity of GM1 on CD4+ T cells from patients with SLE was significantly higher than those from healthy controls, but not on CD8+ T cells. Increased expression of GM1 was more marked on CD4+/CD45RO+ memory T cells from active SLE patients. Patients with SLE showed significantly elevated serum sCD30 and IL-10, but not TNF-alpha levels. In addition, we found that enhanced GM1 expression on CD4+ T cells from patients with SLE positively correlated with high serum levels of sCD30 and IgG as well as disease activity (SLEDAI scores). Our data suggested the potential role of aberrant lipid raft/GM1 on CD4+ T cells and sCD30 in the pathogenesis of SLE.

Ex Vivo Fludarabine Selectively Depletes Human Naive T-Cell Subsets: A Step Toward Modifying Donor Lymphocyte Infusion.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1071-1071
Author(s):  
Melody M. Smith ◽  
Cynthia R. Giver ◽  
Edmund K. Waller ◽  
Christopher R. Flowers
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Ex Vivo ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Naïve T Cell ◽  
Naive T Cell

Abstract Ex vivo modification of donor lymphocytes with purine analogs (mDL) may help to minimize graft versus host disease (GvHD) while providing beneficial graft versus leukemia (GvL) effects. In a murine model system, we have shown that allogeneic donor splenocytes, treated with fludarabine ex vivo have significantly reduced GvHD activity when transferred to irradiated recipient mice, and retain anti-viral and GvL activities (Giver, 2003). This effect appears to be mediated by relative depletion of donor CD4 CD44low, “naive” T-cells. As a first step toward developing mDL for use in patients, we sought to evaluate the effects of ex vivo fludarabine exposure on human T-cell subsets, and to determine the minimum dose of fludarabine required to achieve this effect. Methods: Peripheral blood mononuclear cell samples from 6 healthy volunteers were evaluated at 0, 24, 48, and 72 hour time points after ex vivo incubation in varying dosages of fludarabine: 2, 5, and 10(n=3) mcg/ml. Fludarabine incubated samples were compared to samples that received no fludarabine (untreated). The total viable cell number was determined and the fractions and absolute numbers of viable CD4 and CD8 naïve and memory T-cells were determined using flow cytometry after incubation with 7-AAD (dead cell stain), CD4, CD8, CD45RA, CD62L, and CCR7 antibodies, and measuring the total viable cells/ml. Results: The numbers of viable CD4 and CD8 T-cells remained relatively stable in control cultures. Without fludarabine, the average viability at 72 hr of naive and memory T-cells were 92% and 77% for CD4 and 86% and 63% for CD 8 (Fig. 1A). Naive CD4 T-cells were more sensitive to fludarabine-induced death than memory CD4 cells. At 72 hr, the average viability of fludarabine-treated naive CD4 T-cells was 33% at 2 mcg/ml (8.2X the reduction observed in untreated cells) and 30% at 5 mcg/ml, while memory CD4 T-cells averaged 47% viability at 2 mcg/ml (2.3X the reduction observed in untreated cells) (Fig. 1B) and 38% at 5 mcg/ml. The average viability of naive CD8 T-cells at 72 hr was 27% at 2 mcg/ml and 20% at 5 mcg/ml, while memory CD8 T-cell viability was 22% at 2 mcg/ml and 17% at 5 mcg/ml. Analyses on central memory, effector memory, and Temra T-cells, and B-cell and dendritic cell subsets are ongoing. The 5 and 10 mcg/ml doses also yielded similar results in 3 initial subjects, suggesting that 2 mcg/ml or a lower dose of fludarabine is sufficient to achieve relative depletion of the naive T-cell subset. Conclusions: Future work will determine the minimal dose of fludarabine to achieve this effect, test the feasibility of using ex vivo nucleoside analog incubation to reduce alloreactivity in samples from patient/donor pairs, and determine the maximum tolerated dose of mDL in a phase 1 clinical trial with patients at high risk for relapse and infectious complications following allogeneic transplantation. Figure Figure

Immunomodulatory Drugs Restore Effector Cell Immune Functions In Myeloma Patients With Low Disease Burden After Autologous Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3214-3214 ◽  
Author(s):  
Karel Fostier ◽  
Jurgen Corthals ◽  
Carlo Heirman ◽  
Joeri L. Aerts ◽  
Kris Thielemans ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Disease Burden ◽  
Effector Cell ◽  
Culture Medium ◽  
Tnf Alpha ◽  
Dendritic Cell Vaccination ◽  
Immunomodulatory Drugs ◽  
Ifn Gamma

Abstract The micro-environment in multiple myeloma (MM) is highly immunosuppressive with increased numbers of regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) favoring tumorcell survival and hampering immunotherapeutic strategies such as dendritic cell vaccination. Immunomodulatory drugs (IMiDs) are known to enhance T- and NK-cell function. In this study we evaluated the effects of low dose (0.5 microM) lenalidomide (Len) and pomalidomide (Pom) on the functionality of CD8+ and CD4+ T cells, MDSCs, Tregs and ex-vivo generated mononuclear derived dendritic cells (moDCs) obtained from MM patients after first autologous stem cell transplantation (ASCT). Peripheral blood mononuclear cell fractions were obtained by leukapheresis from 9 MM patients (age 29-62 years), in very good partial response (4/9) or complete response (5/9) after ASCT. The magnitude of cytokine release (mean +/- standard error of the mean, in ng/ml) by purified CD8+ T cells after 144 hours stimulation with anti-CD3/anti-CD28 coated microbeads was significantly increased after addition of Len and Pom to the culture medium, respectively : IFN-gamma (217.5 +/- 62.1 and 437.1 +/- 137.1** vs 66.4 +/- 21.0) , TNF-alpha (21.4 +/- 5.4 and 44.9 +/- 9.4*** vs 4.9 +/- 1.7) and IL-2 (5.3 +/- 2.7 and 12.7 +/- 6.6 vs 1.9 +/- 1.7 ng/ml) (** p< 0.01, *** p< 0.001). We also evaluated the number of different types of cytokines/chemokines on a per cell basis by intracellular flow cytometry staining for IFN-gamma, TNF-alpha, IL-2 and MIP-1beta and observed increased polyfunctionality of CD8+ and CD4+ T cells. After 72 h of stimulation with anti-CD3/CD28 microbeads the number of single, double, triple or quadruple functional CD8+ T cells increased from 5.96 %, 2.82 %, 0.1 %, 0 % (culture medium alone) to 9.68 %, 7.57 %, 0.41%, 0.03 % (Len) and 12.57 %, 8.96 %, 0.81 %, 0.03 % (Pom), respectively. A similar observation was made for CD4+ T cells. A significant percentage, median 5.7 % (4.0-7.2 %) of CD4+ CD25high CD127low (Tregs) was found in the CD4+ T cell population in 8 out of 9 patients, demonstrating the highly suppressive immune environment in myeloma patients even with low disease burden. Effector T cells (Teffs) were stimulated with anti-CD3/CD28 microbeads and cocultured at varying ratios with purified Tregs. After 144 h of coculture, Len and Pom reduced the suppressive effects of Tregs on Teffs proliferation and IFN-gamma and TNF-alpha production (see figure). A similar effect was observed for MDSC but did not reach statistical significance (data not shown). TriMix DCs (moDCs matured by electroporation with mRNA encoding TLR4, CD40L and CD70) and cytokine matured moDCs were cocultured with autologous CD4+ and CD8+ T cells and anti-CD3 microbeads. Adding IMiDs resulted in more polyfunctional CD4+ and CD8+ T cells with both types of DCs but effects were most pronounced with the TriMix variant. Our study shows that Len and Pom restore effector cell functions in myeloma patients with low tumor burden after ASCT. These findings provide a immunomechanistic explanation for IMiD-based maintenance therapy. They also offer a rationale to combine IMiD-based maintenance with immunotherapeutic approaches such as dendritic cell vaccination in this particular setting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CD8+CD44hi but not CD4+CD44hi memory T cells mediate potent graft antilymphoma activity without GVHD

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3230-3239 ◽  
Author(s):  
Suparna Dutt ◽  
Jeanette Baker ◽  
Holbrook E. Kohrt ◽  
Neeraja Kambham ◽  
Mrinmoy Sanyal ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Cell Subset ◽  
B Cell Lymphoma ◽  
Effector Memory ◽  
T Cell Subset ◽  
Progressive Growth

Abstract Allogeneic hematopoietic cell transplantation can be curative in patients with leukemia and lymphoma. However, progressive growth of malignant cells, relapse after transplantation, and graft-versus-host disease (GVHD) remain important problems. The goal of the current murine study was to select a freshly isolated donor T-cell subset for infusion that separates antilymphoma activity from GVHD, and to determine whether the selected subset could effectively prevent or treat progressive growth of a naturally occurring B-cell lymphoma (BCL1) without GVHD after recipients were given T cell–depleted bone marrow transplantations from major histocompatibility complex–mismatched donors. Lethal GVHD was observed when total T cells, naive CD4+ T cells, or naive CD8+ T cells were used. Memory CD4+CD44hi and CD8+CD44hi T cells containing both central and effector memory cells did not induce lethal GVHD, but only memory CD8+ T cells had potent antilymphoma activity and promoted complete chimerism. Infusion of CD8+ memory T cells after transplantation was able to eradicate the BCL1 lymphoma even after progressive growth without inducing severe GVHD. In conclusion, the memory CD8+ T-cell subset separated graft antilymphoma activity from GVHD more effectively than naive T cells, memory CD4+ T cells, or memory total T cells.

scholarly journals Induction of memory-like CD8 + T cells and CD4 + T cells from human naïve T cells in culture

2021 ◽  
Author(s):  
Yasuhito Tokumoto ◽  
Yasuto Araki ◽  
Yusuke Narizuka ◽  
Yosuke Mizuno ◽  
Susumu Ohshima ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Quiescent State ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cells In Culture ◽  
Human T Cells

Abstract Memory T cells are crucial players in vertebrate adaptive immunity but their development is incompletely understood. Here we describe a method to produce human memory-like T cells from naïve human T cells in culture. Using commercially available human T cell differentiation kits, both purified naïve CD8 + T cells and purified naïve CD4 + T cells were activated via T cell receptor signaling and appropriate cytokines for several days in culture. All the T cell activators were then removed from the medium and the cultures were continued in hypoxic condition (1% O2 atmosphere) for several more days; during this period, most of the cells died, but some survived in a quiescent state for a month. The survivors had small round cell bodies, expressed differentiation markers characteristic of memory T cells and restarted proliferation when the T cell activators were added back. We could also induce memory-like T cells from naïve human T cells without hypoxia, if we froze the activated T cells or prepared the naïve T cells from chilled filter buffy coats.

scholarly journals LAG3 and PD1 Regulate CD8+ T Cell in Diffuse Large B-cell Lymphoma Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ying Liu ◽  
Xinhong Guo ◽  
Lingbo Zhan ◽  
Lei Wang ◽  
Xinyou Wang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Checkpoints ◽  
Healthy Controls ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background. Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous lymphoid malignancy. The unsatisfactory outcome for refractory patients has prompted efforts to explore new therapeutic approaches for DLBCL. However, the mechanisms involved in treatment associated with immune checkpoints remain unclear. This study is aimed at investigating the potential roles of programmed cell death protein 1 (PD1) and lymphocyte activation gene 3 (LAG3) in CD8+ T cells for treatment in DLBCL. Methods. Utilizing flow cytometry, we examined the content of T cells, the levels of cytokines, and the expression of PD1 and LAG3 in patients with DLBCL as well as in healthy controls. Levels of cytokines in CD8+ T cells from DLBCL patients before and after treatment were compared by blocking of PD1 and LAG3 in magnetic bead-sorted CD8+ T cells. Results. We found that the proportion of CD4+ T cells and CD8+ T cells was increased in DLBCL patients after treatment. The levels of cytokines trended toward those of healthy controls in treatment. PD1 (+), LAG3 (+), or PD1 (+) LAG3 (+) were all expressed in lower amounts in CD4+ T cells and CD8+ T cells after treatment than in untreated DLBCL patients. In addition, blockade of PD1 and LAG3 in sorted CD8+ T cells markedly inhibited cytokine production in response to treatment. Conclusion. PD1 and LAG3 in CD8+ T cells may be important targets of therapy and play therapeutic role in patients with DLBCL.

scholarly journals Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19

2020 ◽  
Author(s):  
Hasi Chaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ ◽  
Circulating Cytokines

To investigate the immune status of people who previously had COVID-19 infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%) and IL-17 (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

scholarly journals Soluble IL-2Rα facilitates IL-2–mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma

Blood ◽  
2011 ◽  
Vol 118 (10) ◽  
pp. 2809-2820 ◽  
Author(s):  
Zhi-Zhang Yang ◽  
Deanna M. Grote ◽  
Steven C. Ziesmer ◽  
Michelle K. Manske ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cd4 T Cells ◽  
Poor Prognosis ◽  
Elevated Serum ◽  
Foxp3 Expression ◽  
Soluble Form ◽  
Activated T Cells ◽  
Non Hodgkin Lymphoma

Abstract Elevated serum levels of the soluble form of IL-2 receptor α (sIL-2Rα) have been correlated with a poor prognosis in a variety of different types of cancers. However, its biologic relevance remains unclear and controversial. In patients with follicular B-cell non-Hodgkin lymphoma (FL), we observed that serum sIL-2Rα levels were elevated compared with controls and that elevated sIL-2Rα levels before treatment were associated with a poor outcome. To explore the mechanism by which sIL-2Rα may contribute to a poor prognosis in FL, we determined the effects of sIL-2Rα on IL-2 signaling and found that the sIL-2Rα–IL-2 complex promoted T-cell differentiation toward to inhibitory Treg cells rather than TH1 or TH17 cells. Shed by activated T cells that express membrane-bound IL-2Rα, sIL-2Rα further enhanced IL-2–mediated phosphorylation of Stat5 thereby significantly up-regulating Foxp3 expression in CD4+ T cells. We found that CD4+ T cells treated with either IL-2 or sIL-2Rα–IL-2 complex, but not with sIL-2Rα alone, inhibited the function of CD8+ T cells. Taken together, these results indicate that sIL-2Rα actually plays an active biologic role in FL by binding IL-2 and promoting IL-2 signaling rather than depleting IL-2 and blocking its function.

Elevated Expression of T-Cell Immunoglobulin and Mucin Domain 3 on T Cells from Peripheral Blood in Patients with Cervical Carcinoma

2020 ◽  
pp. 1-8
Author(s):  
Juan Li ◽  
Xiao-fei Sun ◽  
Ying Shen ◽  
Qing Yang ◽  
Shu-yan Dai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cervical Carcinoma ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Control Group ◽  
Healthy Controls ◽  
Novel Therapy ◽  
Domain 3

<b><i>Objective:</i></b> To investigate the expression of T-cell immunoglobulin and mucin domain 3 (TIM-3) on peripheral T cells of cervical carcinoma patients. <b><i>Methods:</i></b> Peripheral blood samples from 15 high-grade cervical squamous intraepithelial lesion (HSIL) patients, 24 cervical carcinoma patients, and 21 healthy controls were collected. TIM-3 expressions on the surface of peripheral CD4+ T cells and CD8+ T cells were analyzed with flow cytometry. <b><i>Results:</i></b> There was significantly lower expression of CD4+ T cells and CD8+ T cells in HSIL patients and cervical carcinoma patients compared with healthy controls. We also found that TIM-3 expression on peripheral CD4+ T and CD8+ T cells of both HSIL patients and cervical carcinoma patients was significantly increased compared to the control group. Further analyses revealed that the expression of TIM-3 on peripheral CD4+ T and CD8+ T cells significantly increased in stage III–IV cervical carcinoma patients compared to stages I–II. <b><i>Conclusion:</i></b> The increased expression of TIM-3 on CD4+ T cells and CD8+ T cells of patients with cervical carcinoma and HSIL suggests the potential role of TIM-3 in the development and progression of cervical carcinoma, which may be a novel therapy target for cervical carcinoma.

Determination of CD4+ and CD8+ T cells in the peripheral blood of dogs with demodicosis

Parasitology ◽  
2010 ◽  
Vol 137 (13) ◽  
pp. 1921-1924 ◽  
Author(s):  
S. K. SINGH ◽  
U. DIMRI ◽  
M. C. SHARMA ◽  
B. SHARMA ◽  
M. SAXENA
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Significant Alteration ◽  
Healthy Controls ◽  
Healthy Dogs

SUMMARYThe aim of this study was to evaluate the CD4+/CD8+ ratio in peripheral blood of dogs with localized and generalized demodicosis. Sixteen dogs were examined, 8 with localized and 8 with generalized demodicosis, while 8 healthy dogs were used as controls. Peripheral blood was obtained and CD4+ and CD8+ T cells were determined by flow cytometry. Significantly higher numbers of CD8+ T cells and lower numbers of CD4+ T cells were found in dogs with generalized demodicosis compared to dogs with localized demodicosis and healthy controls. Significantly higher numbers of CD8+ T cells and lower numbers of CD4+ T cells were also found in dogs with localized demodicosis compared to healthy controls. The CD4+/CD8+ ratio was also found to be significantly lower in dogs with generalized demodicosis in comparison with dogs with localized demodicosis and healthy controls. It is concluded that significant alteration in the CD4+/CD8+ ratio may be implicated in the pathogenesis of generalized canine demodicosis.

scholarly journals POS0010 CD38+ MEMORY T CELLS ARE A FUNCTIONALLY DISTINCT SUBSET THAT IS EXPANDED IN SLE AND ASSOCIATED WITH LUPUS NEPHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 207.1-207
Author(s):  
L. Ostendorf ◽  
P. Garantziotis ◽  
D. L. Wagner ◽  
P. Durek ◽  
F. Heinrich ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Cd8 T Cells ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Healthy Controls ◽  
Proliferative Capacity ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Background:We recently reported the beneficial clinical responses of the anti-CD38 monoclonal antibody daratumumab in two patients with systemic lupus erythematosus (SLE) [1]. While the primary rationale for its use was the depletion of autoantibody-producing long-lived plasma cells, daratumumab may promote additional therapeutic effects on CD38-expressing T cells, but their origin, lifestyle and role in lupus pathophysiology remains elusive.Objectives:To investigate the phenotype, transcriptional program, functional properties and clinical associations of CD4+ and CD8+CD38+ memory T cells in SLE compared to healthy controls (HC).Methods:CD38-expression on memory T cell subsets was measured by flow cytometry in 65 patients with SLE and 28 healthy controls. We investigated the functional capacity of CD38+ T cells using CFSE staining and intracellular cytokine staining after polyclonal stimulation. Additionally, we performed single-cell transcriptome and T-cell-receptor sequencing of 7 SLE patients and 7 matched healthy controls, including surface protein expression analysis using CITE-seq (RNA-barcoded) antibodies.Results:Compared to healthy controls, the frequency of CD38-expressing memory T cells in SLE was significantly increased in both CD4+ and CD8+ T cells. SLE patients with a previous or current lupus nephritis had significantly increased levels of CD8+CD38+ memory T cells compared to those without history of renal involvement. CD38+ memory T cells expressed increased levels of Ki-67 and displayed higher proliferative capacity upon polyclonal stimulation than their CD38- counterparts, both in SLE patients and HC, while they showed decreased ability to secrete IFN-γ, IL-2, GM-CSF and TNF-α. Single-cell transcriptome sequencing revealed that CD8+CD38+ memory T cells were enriched within terminally differentiated, cytotoxic CD8 T cells, and had reduced TCR repertoire diversity compared to their CD38- counterparts. CD8+CD38+ memory T cells from SLE patients had significantly higher expression of type I interferon associated genes, both compared to CD38- memory T cells from SLE patients and CD38+ cells from HCs.Conclusion:CD38+ memory T cells with increased proliferative capacity but altered effector functions are significantly expanded in peripheral blood of SLE and correlate with the lupus nephritis. Although the factors mediating their generation and their precise role in the disease pathophysiology remain to be investigated, CD38-expressing T cells may be useful as a future biomarker for lupus nephritis.References:[1]Ostendorf L, Burns M, Durek P, Heinz GA, Heinrich F, Garantziotis P, et al. Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2020 Sep 17;383(12):1149–55.[2]Katsuyama E, Suarez-Fueyo A, Bradley SJ, Mizui M, Marin AV, Mulki L, et al. The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections. Cell Reports. 2020 Jan;30(1):112-123.e4.Acknowledgements:We thank our patients and healthy controls for making our research possible.Disclosure of Interests:None declared.

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