scholarly journals B-CELL DEPLETION WITH ANTI-CD20 MAB EXACERBATES ANTI-DONOR CD4 POSITIVE T-CELL RESPONSES IN HIGHLY SENSITIZED TRANSPLANT MODEL

2020 ◽  
Vol 104 (S3) ◽  
pp. S121-S121
Author(s):  
Asuka Tanaka ◽  
Kentaro Ide ◽  
Yuka Tanaka ◽  
Masahiro Ohira ◽  
Hiroyuki Tahara ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Responses ◽  
Anti Cd20 ◽  
Transplant Model

scholarly journals B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asuka Tanaka ◽  
Kentaro Ide ◽  
Yuka Tanaka ◽  
Masahiro Ohira ◽  
Hiroyuki Tahara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Anti Cd20

AbstractPretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients’ immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4+ T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4+ T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4+ T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4+ T cell response. The depletion of the CD5+ B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10+ CD5+ B cells suppress the excessive response of anti-donor CD4+ T cells responses in sensitized recipients.

scholarly journals B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation

2015 ◽  
Vol 16 (2) ◽  
pp. 672-678 ◽  
Author(s):  
J. Marino ◽  
J. T. Paster ◽  
A. Trowell ◽  
L. Maxwell ◽  
K. H. Briggs ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Memory T Cell ◽  
Cell Responses ◽  
Cd20 Antibody ◽  
Anti Cd20

scholarly journals Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression

2021 ◽  
pp. annrheumdis-2021-220626
Author(s):  
Maria Prendecki ◽  
Candice Clarke ◽  
Helena Edwards ◽  
Stacey McIntyre ◽  
Paige Mortimer ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Glomerular Diseases ◽  
Cell Responses ◽  
The Impact ◽  
Dose Vaccine

ObjectiveThere is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination.MethodsSerological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases.ResultsFollowing first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.

scholarly journals SARS-CoV-2 Spike-Specific T-Cell Responses in Patients With B-Cell Depletion Who Received Chimeric Antigen Receptor T-Cell Treatments

JAMA Oncology ◽  
2021 ◽  
Author(s):  
Kalpana Parvathaneni ◽  
Kyabeth Torres-Rodriguez ◽  
Wenzhao Meng ◽  
Wei-Ting Hwang ◽  
Noelle Frey ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Responses

scholarly journals Contrasting effects of B cell depletion on CD4 + and CD8 + memory T cell responses generated after transplantation

2020 ◽  
Vol 20 (9) ◽  
pp. 2551-2558
Author(s):  
Jose Marino ◽  
Bruno Gonzalez‐Nolasco ◽  
Xianding Wang ◽  
William Orent ◽  
Gilles Benichou
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Memory T Cell ◽  
Cell Responses

B Cell Depletion of Naïve Recipients Enhances Graft Reactive T Cell Responses.

2014 ◽  
Vol 98 ◽  
pp. 20
Author(s):  
T. Singh ◽  
K. Jiang ◽  
R. Ippolito ◽  
B. Ramaswami ◽  
F. Lund ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Responses

scholarly journals Suppression of Proteoglycan-Induced Arthritis by Anti-CD20 B Cell Depletion Therapy Is Mediated by Reduction in Autoantibodies and CD4+T Cell Reactivity

2008 ◽  
Vol 180 (7) ◽  
pp. 4994-5003 ◽  
Author(s):  
Keith Hamel ◽  
Paul Doodes ◽  
Yanxia Cao ◽  
Yumei Wang ◽  
Jeffrey Martinson ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cd4 T Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Reactivity ◽  
T Cell Reactivity ◽  
Anti Cd20

scholarly journals Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy.

2021 ◽  
Author(s):  
Sokratis A. Apostolidis ◽  
Mihir Kakara ◽  
Mark M Painter ◽  
Rishi Raj Goel ◽  
Divij Mathew ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Specific Antibody ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Immunosuppressed Patients ◽  
Anti Cd20

SARS-CoV-2 mRNA vaccination in healthy individuals generates effective immune protection against COVID-19. Little is known, however, about the SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses in patients with multiple sclerosis on anti-CD20 (MS-aCD20) monotherapy following SARS-CoV-2 mRNA vaccination. Treatment with aCD20 significantly reduced Spike and RBD specific antibody and memory B cell responses in most patients, an effect that was ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. In contrast, all MS-aCD20 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. However, treatment with aCD20 skewed these responses compromising circulating Tfh responses and augmenting CD8 T cell induction, while largely preserving Th1 priming. These data also revealed underlying features of coordinated immune responses following mRNA vaccination. Specifically, the MS-aCD20 patients who failed to generate anti-RBD IgG had the most severe defect in cTfh cell responses and more robust CD8 T cell responses compared to those who generated anti-RBD IgG, whose T cell responses were more similar to healthy controls. These data define the nature of SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients, and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making, patient education and public health policy for patients treated with aCD20 and other immunosuppressed patients.

scholarly journals Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

2021 ◽  
Author(s):  
Sokratis A. Apostolidis ◽  
Mihir Kakara ◽  
Mark M. Painter ◽  
Rishi R. Goel ◽  
Divij Mathew ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Specific Antibody ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Immunosuppressed Patients ◽  
Anti Cd20

AbstractSARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.

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