Improved T Cell Recovery After Transplantation of CD3/CD19 depleted Haploidentical Stem Cell Grafts in Pediatric Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4652-4652
Author(s):  
Heiko-Manuel Teltschik ◽  
Tobias Feuchtinger ◽  
Matthias Pfeiffer ◽  
Michael Schumm ◽  
Ingo Mueller ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Conflicts Of Interest ◽  
Negative Impact ◽  
Conditioning Regimen ◽  
T Cell Subsets ◽  
Control Group ◽  
T And B Cells ◽  
Haploidentical Transplantation ◽  
Significant Difference

Abstract Abstract 4652 Profound depletion of T and B cells is a fundamental prerequisite for haploidentical transplantation and allows to minimize GvHD despite HLA incompatibility. However, posttransplant recovery of donor derived T cells is delayed after various graft manipulation procedures and may result in severe infections. Methods to improve this recovery are of great importance. Here we present immune reconstitution data in patients who received CD3/CD19 depleted stem cells in combination with melphalan based or standard conditioning regimens. 32 patients with ALL (n=14), AML/MDS (n=17), CML (n=1) were included. T and B cells were directly depleted using antiCD3/antiCD19 coated magnetic microbeads and the CliniMACSTM device. The patients received either TBI or Bu i.v. and OKT3 (n=9) or a reduced intensity conditioning (“RIC”: Mel 140mg/m2, Flud 160mg/m2, TT 10mg/kg, OKT3, n= 23). Absolute numbers of lymphocyte subsets per microliter on day 90 were compared within these both groups and with a historical control group (patients with leukemias who received CD34 selected grafts and TBI or Bu based standard conditioning regimen in combination with ATG, n=28). CD3+4+, CD3+8+ and total numbers of CD3+ of patients after CD3/CD19 depletion were significantly higher in the RIC-group than in the TBI/Bu-group (mean numbers: 85.83 vs. 38.84; 133.46 vs. 19.69; 270.27 vs. 63.99; p<0.05, unpaired t-test). Comparison with the whole CD34 historical group showed a faster recovery of CD3+4+ in patients with CD3/19 depletion and RIC (104.26 vs. 54.22; p= 0,034) but no significant difference in CD3+8+ and CD3+. Furthermore, subgroups of the CD34 historical population were compared: patients with CD3/19 depletion and RIC had a significantly faster recovery of CD3+4+, CD3+8+ and CD3+ than CD34 patients with TBI (104.26vs. 25.48; 133.46vs. 43.17; 270.27 vs. 65.86; p<0.05) but had no advantage over CD34 patients with non-TBI conditioning. Conclusions: the type of graft manipulation appeared to have an influence on the speed of CD4+ recovery (CD3/19 depletion > CD34 selection). Moreover, the use of TBI had a clear negative impact on all T cell subsets: patients with TBI had a slower recovery than patients with non-TBI conditioning, independent from graft manipulation procedures and probably due to thymic damage. Thus, the use of RIC-protocols in combination with CD3/CD19 depletion may help to speed up the immune recovery after haploidentical transplantation. Further studies are warranted to evaluate the risk of relapse. Disclosures: No relevant conflicts of interest to declare.

Comparative Analysis on Cellular Components of Bone Marrow Microenvironment in Normal and Aberrant Hematopoiesis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4808-4808
Author(s):  
Young-Ho Lee ◽  
Young-hee Kwon ◽  
Kyoujung Hwang ◽  
Hyunju Jun ◽  
Byungbae Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Conflicts Of Interest ◽  
T Cell Subsets ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Stromal Cell Derived Factor ◽  
And Control ◽  
Cellular Components

Abstract Abstract 4808 Background: It is now evident that hematopoietic stem cells (HSCs) reside preferentially at the endosteal region within the bone marrow (BM) where bone-lining osteoblasts are a key cellular component of the HSC niche that directly regulates HSC fate. We investigated the microenvironmental differences including osteoblastic activities and HSC components in myeloproliferative (chronic myeloid leukemia, CML) and hypogenerative disease (aplastic anemia, AA) as well as normal control (NC). Methods: The immunohistochemistry for osteonectin, osteocalcin, stromal cell derived factor (SDF, CXCL12), T cell, T helper/inducer cell, T suppressor/cytotoxic cell, hematopoietic stem/progenitor (CD34, CD117) and megakaryocytes was performed on BM biopsy specimens from 10 AA patients, 10 CML patients and 10 NC (lymphoma without BM involvement). The positive cells for immunohistochemical stainings except osteocalcin on each slide were calculated on 10 high power fields (HPF, ×400), and then corrected by the cellularity. The positive cells for osteocalcin were counted on the peritrabecular line on each slide, and then corrected by the mean length measured. Results: The CD34+ cells (p=0.012) and megakaryocytes (p<0.0001) were significantly lower in AA than in NC, but CD117+ cells was comparable in AA, CML, and control samples. The osteonectin+ cells (p=0.0003) were lower in CML than in AA and NC, however the osteocalcin+ cells showed wide variation (0-903/2035um) and no significant difference. The SDF+ cells (p<0.0001) was significantly higher in AA and very lower in CML, compared with NC. The counts for T cell and T cell subsets were significantly lower in CML than in NC, and higher in AA than in NC (p<0.0001). Conclusions: Cellular components of BM microenvironment in 2 hematologic diseases representative of myeloproliferation (CML) and hyporegeneration (AA) respectively are quite different. Further studies would be required to explore the role of these components for hematopoiesis and the rationale for therapeutic application. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Simultaneous analysis of antigen-specific B and T cells after SARS-CoV-2 infection and vaccination

2021 ◽  
Author(s):  
Krista L Newell ◽  
Mitchell J Waldran ◽  
Stephen J Thomas ◽  
Timothy P Endy ◽  
Adam Tully Waickman
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
B Cells ◽  
Simultaneous Detection ◽  
T Cell Subsets ◽  
Cell Populations ◽  
T And B Cells ◽  
Simultaneous Identification ◽  
Immune Profiling ◽  
Insight Into

Conventional methods for quantifying and phenotyping antigen-specific lymphocytes can rapidly deplete irreplaceable specimens. This is due to the fact that antigen-specific T and B cells have historically been analyzed in independent assays each requiring millions of cells. A technique that facilitates the simultaneous detection of antigen-specific T and B cells would allow for more thorough immune profiling with significantly reduced sample requirements. To this end, we developed the B And T cell Tandem Lymphocyte Evaluation (BATTLE) assay, which allows for the simultaneous identification of SARS-CoV-2 Spike reactive T and B cells using an optimized Activation Induced Marker (AIM) T cell assay and dual-color B cell antigen probes. Using this assay, we demonstrate that antigen-specific B and T cell subsets can be identified simultaneously using conventional flow cytometry platforms and provide insight into the differential effects of mRNA vaccination on B and T cell populations following natural SARS-CoV-2 infection.

scholarly journals Clinical Observation of the Number of Lymphocytes and T Cell Subsets in Patients with COVID-19 at Different Stages

2020 ◽  
Author(s):  
Jing Bai ◽  
Hui Zhou ◽  
Bao-sheng Dai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
White Blood Cells ◽  
Peripheral Blood Lymphocytes ◽  
T Cell Subsets ◽  
Control Group ◽  
Cd8 Cells ◽  
Significant Difference ◽  
Severe Group

Abstract To explore the changes of lymphocytes and T cell subsets at different stages in patients with COVID-19. 86 patients with COVID-19 were enrolled, and the dynamic changes of peripheral blood lymphocytes and T cell subsets of CD3+, CD4+, and CD8+ were measured on admission, after treatment for1 week, 2 weeks, and before discharge. There were no significant differences in the number of white blood cells and lymphocytes between admission and 2 weeks after treatment or before discharge in severe patients. The counts of CD3+, CD4+, and CD8+ T cells decreased significantly on admission. After 2 weeks of treatment, the CD3+ counts were significantly higher than that on admission. The CD4+ and CD8+ counts increased significantly after 1 week of treatment, and went up remarkably before discharge compared with that on admission. There was no significant difference in the number of CD3+ cells between the mild group and the control group on admission, but it was significantly lower in the severe group than that in the control group and the mild group. The CD4+ and CD8+ counts decreased significantly in both mild and severe patients on admission, and increased significantly before discharge. At the time of discharge, the CD4+ counts in the severe and mild groups were still significantly lower than in the control group, but there was no significant difference in CD8+ counts among the three groups. The counts of CD3+,CD4+,and CD8+ T cells in the patients with COVID-19 is significantly correlated with the short-term prognosis, and is more sensitive than lymphocytes. In the earliest stage, the numbers of CD4+ and CD8+ cells are more sensitive to early reduction and faster to late recovery.

HLA-E restricted CD8+ T cell subsets are phenotypically altered in multiple sclerosis patients

2013 ◽  
Vol 20 (7) ◽  
pp. 790-801 ◽  
Author(s):  
Kim Pannemans ◽  
Bieke Broux ◽  
An Goris ◽  
Bénédicte Dubois ◽  
Tom Broekmans ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Subsets ◽  
Regulatory Role ◽  
T And B Cells ◽  
Autoreactive T Cell ◽  
Multiple Sclerosis Patients

Background: The importance of Qa-1 restricted CD8+ T cells in regulating autoreactive T cell responses has been demonstrated in animal models for autoimmune disorders, including multiple sclerosis (MS). Objective: We hypothesize that their human variant, HLA-E restricted CD8+ T cells, fulfills a similar regulatory role in man and that these cells are of importance in MS. Methods: A large cohort of MS patients and healthy controls was genotyped for the two known HLA-E polymorphisms. Flow cytometry was used to determine HLA-E expression kinetics and to phenotype HLA-E restricted CD8+ T cells. Immunohistochemistry was performed to investigate HLA-E expression in the central nervous system (CNS) of MS patients. Results: HLA-E is upregulated on immune cells upon in vitro activation and this upregulation is polymorphism-dependent for T and B cells. T and B cells in lesions of MS patients show enhanced HLA-E expression. Furthermore, NKG2C+CD8+ T cells of MS patients have a significantly lower Foxp3 expression, while NKG2A+CD8+ T cells of MS patients produce higher levels of pro-inflammatory cytokines compared to those of healthy individuals. Conclusion: Our study indicates that the HLA-E system is altered in MS and could play a regulatory role in disease.

Permissive HLA-DPB1 Mismatching Compared to a Non-Permissive Mismatching Significantly Improves Overall Survival Following Allogeneic Transplantation In Patients with Both 10/10 and 9/10 Matched Unrelated Donors

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 227-227 ◽  
Author(s):  
Bronwen E. Shaw ◽  
Katharina Fleischhauer ◽  
Mari Malkki ◽  
Theodore Gooley ◽  
Elisabetta Zino ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Matched Pairs ◽  
Significant Difference ◽  
Unrelated Donors ◽  
Matching Criteria

Abstract Abstract 227 It is well established that the use of a donor matched for 9–10/10 alleles at HLA-A,-B,-C,-DRB1,-DQB1 significantly improves overall survival (OS) after unrelated donor (UD) haematopoietic stem cell transplantation (HSCT). Whilst the matching status for HLA-DPB1 alleles has been shown to influence transplant complications (relapse and graft-versus-host disease (GVHD), its impact on survival has not been well defined. The current unmet need in clinical practice is an approach to stratify selection criteria when a clinician is confronted with the choice between several 10/10 or 9/10 matched unrelated donors. There is now considerable interest in exploring different types of matching criteria to define permissive HLA-DPB1 mismatches which may be associated with an improved outcome. We have previously shown that HLA-DPB1 permissiveness can be functionally defined by the characterization of shared T cell epitopes (TCE) recognized by alloreactive T cells. In this model, allelic HLA mismatches are classified as permissive if they do not involve TCE disparities, and as non-permissive if they do. Using this concept, we developed two overlapping algorithms of permissivity for allelic HLA-DPB1 mismatches, on the basis of 3 (TCE3) or 4 (TCE4) groups of DPB1 alleles encoding immunogenic TCE. Data from relatively small prospective studies has shown a worse outcome to be associated with non-permissive DPB1 TCE disparities. Here, we present outcomes in 9123 UD-HSCT pairs, collected through the International Histocompatibility Working Group (IHWG). The cohort was comprised of 5809 10/10 matched transplant pairs and 3314 9/10 matched pairs. Within the 10/10 and 9/10 matched pairs three groups of patients were identified: 1. Zero DPB1 mismatches (i.e. allele matched), 2. Permissive DPB1 mismatch, 3. Non-permissive DPB1 mismatch. The model was adjusted for disease severity, source of stem cells, conditioning regimen, use of T-cell depletion, patient/donor gender and patient age. In line with DPB1 allele frequencies in worldwide populations, the number of transplants scored as permissive was higher for TCE3 (4398/7270 [60.4%]) than for TCE4 (2577/7270 [35.4%]). Using the DPB1 permissive mismatch transplants as the reference group (either 10/10 or 9/10 matched), we showed that DPB1 allelic matches resulted in similar survivals to DPB1 permissive mismatches, both in the 10/10 (HR 0.96, p=0.498 for TCE3 and HR 0.99, p=0.85 for TCE4) and the 9/10 setting (HR 0.97, p=0.70 for TCE3 and HR 0.99, p=0.96 for TCE4). In contrast, survival was significantly worse in the presence of a non-permissive TCE3 or TCE4 mismatch, both in the 10/10 (HR 1.15, p=0.0005 for TCE3 and HR 1.13, p=0.0035 for TCE4) and in the 9/10 matched setting (HR 1.13, p=0.0140 for TCE3 and HR 1.11, p=0.0448 for TCE4). The survival detriment appeared to be due to a significantly increased non-relapse mortality (TCE3: 10/10 HR 1.27, p<0.001 and 9/10 HR 1.21, p=0.0001; TCE4: 10/10 HR 1.24, p<0.001 and 9/10 HR 1.13, p=0.0514), as well as an increase in grades II-IV acute GVHD (TCE3: 10/10 HR 1.17, p<0.001 and 9/10 HR 1.29, p<0.001; TCE4: 10/10 HR 1.12, p=0.0035 and 9/10 HR 1.19, p<0.0001). There was no significant difference in disease relapse between permissive and non-permissive mismatched pairs. Finally, using the 10/10 DPB1 permissive mismatched group as a reference, we found survival to be similar for 10/10 DPB1 non-permissive (HR 1.15) and 9/10 DPB1 permissive (HR 1.20) or DPB1 allele matched (HR 1.17) transplants. In conclusion, our results suggest that extending donor selection to include HLA-DPB1 both allelic and functional TCE matching may result in better prediction of survival for patients. These findings provide an attractive new algorithm to stratify donor choice when several well-matched UD are identified. Disclosures: No relevant conflicts of interest to declare.

Improved Early Outcomes with T-Cell Replete (TCR) Compared with T-Cell Depleted (TCD) Haploidentical Stem Cell Transplantation (HaploSCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 320-320 ◽  
Author(s):  
Stefan O Ciurea ◽  
Rima M. Saliba ◽  
Ulas D. Bayraktar ◽  
Susan Xie ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
T Cell Subsets ◽  
High Dose ◽  
Cd4 Cells ◽  
Post Transplant ◽  
Cd34 Cells ◽  
Immunologic Reconstitution

Abstract Abstract 320 Background: HaploSCT has been commonly performed with a TCD graft using CD34+ selection; however, this has been limited by a higher non-relapse mortality (NRM) primarily related to infectious complications. An alternative approach using a TCR bone marrow graft and high-dose post-transplant cyclophosphamide (HDPTCy) in the setting of non-myeloablative conditioning has been reported to have lower NRM and acceptable rates of GVHD. Methods: We hypothesized that TCR HaploSCT using HDPTCy is associated with improved immunologic reconstitution, less NRM and better early outcomes compared with TCD HaploSCT, and analyzed 65 consecutive patients (pts) treated at UTMDACC with the same conditioning regimen, fludarabine (40mg/m2/day × 4), melphalan (140mg/m2) and thiotepa (10mg/kg). TCD HaploSCT pts were treated between 2001 and 2009, while TCR patients after 2009. 6 pts in the TCR group >55 years/comorbidities received reduced doses of melphalan (100mg/m2) and thiotepa (5mg/kg). There was no GVHD prophylaxis in the TCD group, while TCR group received HDPTCy (50mg/kg/day × 2) followed by tacrolimus and mycophenolate. Results: The median follow-up was 10 months (range 3.5–25) for the TCR group and 44 (11–79) months for the TCD group. Median age was 45 years (range 20–63) in the TCR group and 36 years (range 18–56) in the TCD group (p=0.02). 28% were > 50 years in the TCR compared with 6% in the TCD group (p=0.02). Diagnoses were: AML/MDS 50% vs. 79%, ALL 13% vs. 12%, CML 16% vs. 6%, lymphoma/CLL 9% vs. 3% in the TCR vs. TCD groups, respectively. Only 13 (41%) and 12 (36%) of pts were in remission at transplant in both groups, respectively (p=0.7). 10/16 (62.5%) pts with AML/MDS in the TCR group had poor risk cytogenetics vs. 13/26 (50%) pts in the TCD group. The donors were 5/10 allele match in 20/32 (63%) and 16/31 (52%) in the two groups, respectively. Median numbers of CD34+ cells infused were 2.5×10e6/kg in the TCR group and 10.5×10e6/kg in the TCD group. All pts in the TCD group had peripheral blood selected CD34+ cells while all but one received bone marrow stem cells in the TCR group. One pt had early death in each group. Primary engraftment was achieved in 94% in the TCR group and 81% in the TCD group (p=0.1). Day-100 NRM for all pts was 9% in the TCR group vs. 21% for the TCD group, and for pts in remission at transplant 0% vs. 42%, respectively (p=0.01). NRM at 1 year for all pts was 16% for the TCR group vs. 42% for the TCD group (p=0.03) (Figure1), while for pts in remission was 0% vs. 67% (p=0.001). The cumulative incidences of grade II-IV aGVHD was 27% vs. 11% (p=0.5) and cGVHD was 8% vs. 18%, in the TCR and TCD group, respectively (p=0.03). OS and PFS at 1 year post-transplant were 66% vs. 30% (p=0.02) and 45% vs. 21% (p=0.03) for the whole group, and 92% vs. 33% (p=0.03) and 80% vs. 25% (p=0.02) for pts in remission at transplant, respectively (Figure1). Improved NRM in the TCR group was related to significantly better immunologic reconstitution of T-cell subsets. On day 30 post transplant there was a significantly better recovery of absolute CD4 cells in the TCR group (median 24 vs. 2, p=0.004) and CD8 cells (median 20.5 vs. 1.5, p=0.036). CD4 cells remained significantly lower in the TCD group until after day 180 when the median CD4 count was 200.5 vs. 64 in the TCR group (p=0.04) while the difference in CD8 counts became non-significantly higher in the TCR after day 90 (median 119 vs. 29, p=0.23). Conclusion: TCR HaploSCT is associated with better immunologic reconstitution and improved early outcomes compared with TCD HaploSCT. Disclosures: No relevant conflicts of interest to declare.

CD34+ Selected Hematopoietic Cell Boosts (HCB) for Treatment of Refractory Cytopenia Following T-Replete HLA-Haploidentical Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Asad Bashey ◽  
Xu Zhang ◽  
Lawrence E Morris ◽  
H. Kent Holland ◽  
Scott R. Solomon ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Infections ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Patient Characteristics ◽  
Hematopoietic Cell ◽  
Maximal Increase ◽  
Haploidentical Transplantation

HLA-haploidentical donor transplants using T-replete grafts and posttransplant cyclophosphamide (HIDT) are increasingly utilized and have helped address the shortage of donors particularly among minority populations. While HIDT seem to produce similar survival outcomes to matched donor transplants, they may be subject to higher rates of early reactivation of some viruses. Myelosuppressive treatments for these viruses, other microbial infections and GVHD may produce prolonged periods of poor hematopoietic function and resulting cytopenia. Additional infusion of hematopoietic cells from the patient's donor that are ex-vivo depleted of T-cells, may help ameliorate these cytopenias and need for transfusions. Between June 2017 and June 2019 we performed 82 first HIDT at our center. Of these, seven patients (8.5%) underwent a T-cell depleted hematopoietic cell boost (HCB) following remobilization and collection of PBSC from the original donor in to correct refractory cytopenias. Patients were required to have &gt;80% donor T-cell chimerism and have multilineage severe cytopenias for greater than three weeks after demonstrating prior engraftment. Active GVHD was not a contraindication to HCB. Patient characteristics were: Median age 69 (29-74); sex M4, F3; diagnoses - AML 3, NHL1, MPN 1, HL 1, SCD 1; prior autotransplant -2; regimen intensity of transplant - non-myeloablative -6, myeloablatve 1; median CD34 and CD3 doses of the original transplant were -5.01 (2.89-7.58) x 106/kg and 20.88 (3.7-41.6) x 107/kg respectively. All patients had 100% donor CD3 + cell and CD33+ cell chimerism in peripheral immediately prior to HCB. Median time between transplant and HCB was303 days (range 144-1048). Maximum grade acute GVHD and chronic GVHD pre-HCB were - gd 1(1), gd 2(3) gd 3(1) and severe chronic (1 patient). Four patients had active GVHD requiring systemic treatment at the time of HCB. Documented viral infections pre-HCB were: RTI- influenza (2) Parainfluenza(2), RSV(2) coronavirus(2) metapneumovirus(1) rhinovirus (1), adenovirus (1), HHV6 (1); Blood- CMV (3) adenovirus (3), HHV6 (1); Urine BKV (4). Original donors underwent repeat PBSC mobilization using G-CSF and leukapheresis targeting &gt; 5 x 106 CD34 cells/kg. collection. The PBSC collection was CD34+ cell selected using a Miltenyi column (CliniMACS Plus CD34+ System) targeting &lt; 1 x 105 CD3 cells/kg in the final product. No additional conditioning regimen was administered prior to HCB. Median doses infused for the HCB were CD34+ 4.89 x 106/kg (range 2.3-11.7) and CD3+ 0.21 x 105/kg (range 0.07-0.6). Median follow-up from day of HCB is 18.6m (13.2-37.2m). There were no infusional toxicities. One patient who had gd 1 aGVHD pre-HCB developed gd 3 aGVHD 4m post-HCB. However, this was felt to be related to withdrawal of immunosuppression. No other patient developed new GVHD or exacerbation of pre-existing GVHD. All patients demonstrated an increase in absolute neutrophil count (ANC) , platelet (plat) and hemoglobin (Hb) post HCB (Fig).Median values for maximal increase of ANC, plat and Hb from day of HCB to 60 days post HCB were 1.48 x 109/L, 73 x 109/L and 2.2 g/dL respectively (p&lt;0.05 for all). All patients who were platelet and RBC transfusion dependent pre-HCB became transfusion independent within 60 days post-HCB. These data indicate that HCB using CD34+ cell selected re-mobilized PBSC collections from original haploidentical donor are safe and effective in correcting prolonged severe cytopenias following HIDT. Pre-existing GVHD and ongoing immunosuppressive therapy for GVHD are not a contraindication to their use Figure Disclosures No relevant conflicts of interest to declare.

Impact of Labor on Peripheral Blood Maternal T-Cell Subsets and on Regulatory T and B Cells

2016 ◽  
Vol 24 (2) ◽  
pp. 276-284 ◽  
Author(s):  
Jorge Lima ◽  
Catarina Martins ◽  
Glória Nunes ◽  
Maria-José Sousa ◽  
Jorge C. Branco ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Peripheral Blood ◽  
T Cell Subsets ◽  
T And B Cells

scholarly journals A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement.

1995 ◽  
Vol 181 (6) ◽  
pp. 2007-2015 ◽  
Author(s):  
S Matsuoka ◽  
Y Asano ◽  
K Sano ◽  
H Kishimoto ◽  
I Yamashita ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Death ◽  
T Cell ◽  
B Cells ◽  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Target Cells ◽  
T And B Cells ◽  
Fab Fragments ◽  
T Cell Clone

A monoclonal antibody, RE2, raised by immunizing a rat with cell lysate of a mouse T cell clone, was found to directly kill interleukin 2-dependent T cell clones without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments with anti-rat immunoglobulin reconstituted the cytotoxicity. The cytotoxicity was temperature dependent: the antibody could kill target cells at 37 degrees C but not at 0 degrees C. Sodium azide, ethylenediaminetetraacetic acid, and forskolin did not affect the cytolytic activity of RE2, while the treatment of target cells with cytochalasin B and D completely blocked the activity. This suggested that the cell death involves a cytoskeleton-dependent active process. Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. The antibody also killed T cell lymphomas and T and B cell hybridomas only when these cells were preactivated with concanavalin A, lipopolysaccharide, or phorbol myristate acetate. Preactivated peripheral T and B cells were sensitive to the cytotoxicity of RE2, while resting T and B cells were insensitive. These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation.

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