scholarly journals Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab

Blood ◽  
2009 ◽  
Vol 113 (16) ◽  
pp. 3809-3812 ◽  
Author(s):  
Shannon P. Hilchey ◽  
Ollivier Hyrien ◽  
Tim R. Mosmann ◽  
Alexandra M. Livingstone ◽  
Jonathan W. Friedberg ◽  
...  
Keyword(s):  
T Cell ◽  
Follicular Lymphoma ◽  
Cell Response ◽  
Cellular Response ◽  
T Cell Response ◽  
Passive Immunotherapy ◽  
Cell Kill ◽  
Before And After ◽  
Anti Cd20 ◽  
Universal Application

Abstract The incorporation of rituximab, a chimeric anti-CD20 monoclonal antibody, into the therapeutic armamentarium for patients with follicular lymphoma (FL) has significantly improved treatment outcome for such patients. Despite the almost universal application of this therapy, however, its exact mechanism of action has not been completely defined. One proposed mechanism is that of a “vaccinal” effect, whereby FL cell kill by rituximab results in the elicitation of an FL-specific T-cell response. The demonstration that rituximab can even elicit such a response in patients has, to our knowledge, never been shown. We analyzed the response against the immunoglobulin expressed by the FL before and after rituximab monotherapy in 5 FL patients and found an increase in FL idiotype–specific T cells after rituximab in 4 of 5 patients. Our data thus provide “proof of principle” for the ability of passive immunotherapy with rituximab to elicit an active FL-specific cellular response.

scholarly journals Involvement of the CD27-CD70 co-stimulatory pathway in allogeneic T-cell response to follicular lymphoma cells

1999 ◽  
Vol 106 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Doris Schmitter ◽  
Ursula Bolliger ◽  
Michael Hallek ◽  
Gabriella Pichert
Keyword(s):  
T Cell ◽  
Follicular Lymphoma ◽  
Cell Response ◽  
T Cell Response ◽  
Lymphoma Cells

scholarly journals The CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus Involves the L Antigen: Uncovering New Tricks for an Old Virus

2007 ◽  
Vol 81 (10) ◽  
pp. 4928-4940 ◽  
Author(s):  
Maya F. Kotturi ◽  
Bjoern Peters ◽  
Fernando Buendia-Laysa ◽  
John Sidney ◽  
Carla Oseroff ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Response ◽  
Cellular Response ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
T Cell Response ◽  
Ifn Γ ◽  
Lcmv Infection

ABSTRACT CD8+ T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2b mice. Although antigen-specific responses against LCMV infection are well studied, we found that a significant fraction of the CD8+ CD44hi T-cell response to LCMV in H-2b mice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCMV proteome for gamma interferon (IFN-γ) induction from CD8+ T cells derived from LCMV-infected H-2b mice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8+ CD44hi response. Thus, bystander T-cell activation does not contribute appreciably to the CD8+ CD44hi pool. Strikingly, 15 of the 19 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCMV infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8+ T cells, whereas IFN-γ production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCMV-specific CD8+ T-cell response is more complex than previously appreciated.

scholarly journals Cellular and humoral immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in patients with hematologic malignancies

2021 ◽  
Author(s):  
Moraima Jiménez ◽  
Elisa Roldan ◽  
Candela Fernández- Naval ◽  
Guillermo Villacampa ◽  
Monica Martinez-Gallo ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Response ◽  
Immunosuppressive Agents ◽  
Immunosuppressive Treatment ◽  
Humoral Response ◽  
Hematologic Malignancies ◽  
T Cell Response ◽  
Cell Counts ◽  
Immuno Assay ◽  
Anti Cd20

Recent studies have demonstrated a suboptimal humoral response to SARS-CoV-2 mRNA vaccines in patients diagnosed with hematologic malignancies, however data about cellular immunogenicity is scarce. In this study we aimed to evaluate both the humoral and cellular immunogenicity one month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by the Elecsys and LIAISON Anti-SARS-CoV-2 S assay while T-cell response was assessed by Interferon-Gamma-Release-immuno-Assay technology. Overall, 76.3% (184/241) of patients developed humoral immunity and the cellular response rate was 79% (184/233). Hypogammaglobulinemia, lymphopenia, active hematological treatment and anti-CD20 therapy during the last 6 months were associated with an inferior humoral response. Conversely, age over 65 years, active disease, lymphopenia and immunosuppressive treatment for GvHD were associated with an impaired cellular response. A significant dissociation between humoral and cellular response was observed in patients treated with anti-CD20 therapy, being the humoral response of 17.5% whereas the cellular response was 71.1%. In these patients B-cell aplasia was confirmed while T cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients under immunosuppressive treatment for GvHD, while only 52.4% had cellular response. The cellular and humoral response to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematological malignancies is highly influenced by the presence of treatments like anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

Complementary Presence of HBV-Specific Humoral and T-Cellular Immune Response Provide the Long-Lasting Immune Protection After Neonatal Immunization

2021 ◽  
Author(s):  
Yunmei Huang ◽  
Yuting Yang ◽  
Tingting Wu ◽  
Zhiyu Li ◽  
Yao Zhao
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Hepatitis B ◽  
Cell Response ◽  
Cellular Immune Response ◽  
Cellular Response ◽  
T Cell Response ◽  
Hbv Infection ◽  
Hepatitis B Vaccination ◽  
Cellular Immune

Abstract Background: Hepatitis B vaccination is the most cost-effective way to prevent HBV infection. Currently, hepatitis B vaccine (HepB) efficacy was usually assessed by anti-HBs level, but there were little comprehensive analyses of humoral and cellular immune response to HepB in children after neonatal immunization. Methods: A total of 145 children with primary hepatitis B immunization history were involved in this study to evaluate the efficacy of HepB. Blood samples were obtained from 80 eligible children before one dose of HepB booster and 41 children post-booster. Children with anti-HBs at a low level (<10mIU/mL and [10,100) mIU/mL) were received one dose of HepB booster after informed consent. Subjects were be measured anti-HBs, HBsAg-specific T cell responses and frequency of B cell subsets before and after booster. Results: Among 80 subjects, 81.36% of children showed both T cell and anti-HBs responses positive at baseline. After one dose of booster, anti-HBs titer (P<0.0001), positive rate of HBsAg-specific T cell response (P=0.0036) and magnitude of SFCs (P=0.0003) increased significantly. Comparing preexisting anti-HBs titer <10mIU/mL with anti-HBs titer [10,100) mIU/mL, anti-HBs response (P=0.0005) and HBsAg-specific T lymphocyte response (P<0.0001) increased significantly. The change tendency of HBV specific humoral response is complementary to T cellular response with age. Conclusion: Protection from primary HBV immunization persists long on account of the complementary presence of HBV-specific humoral and T-cellular immune response. One dose of HepB booster is efficient enough to produce protective anti-HBs and enhance HBsAg-specific T cell response. In the HBV endemic areas, HepB booster immunization is still the most economical and effective way to prevent HBV infection, especially in children without anti-HBs.

Rapid T Cell Response to Vaccination Can Occur without Antibody Response in Children Post HSCT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2235-2235
Author(s):  
W. Nicholas Haining ◽  
J. Evans ◽  
N. Seth ◽  
G. Callaway ◽  
K. Wucherpfennig ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Response ◽  
Influenza A ◽  
T Cell Response ◽  
T Cell Memory ◽  
Cell Immunity ◽  
Before And After ◽  
B Cell Response

Abstract Vaccination is widely used to improve pathogen-specific immunity in patients post HSCT, but it is not known whether patients can mount an effective T cell response to vaccine antigens (vAg). Moreover the relationship between T and B cell response to vAg has not been studied. We hypothesized that a sufficiently sensitive assay of T cell response to vAg would allow vaccination to be used as a tool to measure immune recovery post HSCT and improve vaccine design. We therefore: (1) developed a flow-cytometry-based approach to quantify and characterize T cells specific for vAg; (2) validated it by measuring T cell immunity to influenza A in normal donors; and (3) characterized the T and B cell response to influenza vaccination in pediatric HSCT patients. PBMC were labeled with CFSE and stimulated in vitro with whole influenza Ag. Ag-specific T cells were sensitively detected by their proliferation (loss of CFSE fluorescence) and simultaneous expression of the activation marker HLA-DR. Proliferating/active T cells could be readily detected after stimulation with influenza A Ag in healthy adult (n=4) and pediatric (n=19) donors but were absent in control conditions. Both CD4+ and CD8+ T cell proliferation was detected in all donors but one, and in children as young as 6mo. Staining with MHC I- and MHC II-tetramers confirmed that the proliferating/active population contained T cells specific for immunodominant CD8+ and CD4+ epitopes, demonstrating that vAg were processed and presented to epitope-specific T cells. To characterize the phenotype of influenza-specific T cell memory, we separated memory and naive CD4+ cells prior to antigen-stimulation. Antigen-experienced (CD45RA−/CCR7−) but not naive (CD45RA+/CCR7+) T cells proliferated to vAg confirming that the assay detected pre-existing influenza-A-specific T cell memory. We next assessed Influenza-A-specific T cell immunity before and after influenza vaccination in five pediatric HSCT recipients (mean age 10.6y, range 5–15y; mean time from transplant 13m, range 3–21m). Prior to vaccination the CD4 proliferation to influenza-A was a mean of 3.3% (range 0.04–11%). Following vaccination CD4 proliferation increased significantly in all patients (mean 19.0%, range 6.9%–31.8%, p=0.02). This increase was specific as proliferation to control Ag was unchanged. Influenza-A CD8+ proliferation also increased in 3 of 5 patients but was not statistically significant for the group consistent with the limited efficacy of soluble vAg in inducing CD8+ T cell response. All patients had detectable influenza-A-specific IgG levels prior to vaccination but despite a T cell response to vaccination in all patients, none had a significant increase in IgG level following vaccination. Only one patient had an IgM response; this patient also had the highest influenza-A-specific CD4 proliferation before and after immunization suggesting that there may be a threshold of T cell response required for a B cell response. Using a novel assay we demonstrate that a T cell response to vaccination can occur without an accompanying B cell response. This assay provides a more sensitive measure of immunity to vaccination and allows vaccine response to be used as a benchmark of strategies to accelerate post-HSCT T cell reconstitution.

scholarly journals Comparing Humoral and Cellular Adaptive Immunity during Convalescent Phase of COVID-19 in Hemodialysis Patients and Kidney Transplant Recipients

2021 ◽  
Vol 10 (21) ◽  
pp. 4833
Author(s):  
Dorota Kamińska ◽  
Hanna Augustyniak-Bartosik ◽  
Katarzyna Kościelska-Kasprzak ◽  
Marcelina Żabińska ◽  
Dorota Bartoszek ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Kidney Transplant ◽  
Adaptive Immunity ◽  
Cell Response ◽  
Cellular Response ◽  
T Cell Response ◽  
Interferon Gamma Release Assay ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background. It is still unclear whether COVID-19 convalescent kidney transplant recipients (KTR) and hemodialysis (HD) patients can develop anti-SARS-CoV-2 adaptive immunity. The aim was to characterize and compare the immune response to the virus in HD patients and KTR. Methods. The study included 26 HD patients and 54 KTR—both convalescent (14 HD, 25 KTR) and unexposed. The immune response was assessed by determining the anti-SARS-CoV-2 antibodies in serum and specific T cell response via the interferon-gamma release assay (IGRA). Moreover, blood-morphology-derived parameters, immune cell phenotypes, and acute phase reactants were evaluated. Results. KRT and HD convalescents presented similar serum levels of anti-SARS-CoV-2 IgG and IgA. A negative correlation occurred between IgG and time after the infection was observed. There was a strong relationship between the prevalence of anti-SARS-CoV-2 cellular and humoral responses in both groups. Convalescent IGRA response was significantly higher in HD patients compared to KTR. Conclusions. HD patients and KTR develop humoral and cellular responses after COVID-19. The antibodies levels are similar in both groups of patients. SARS-CoV-2-reactive T cell response is stronger in HD patients compared to KTR. The SARS-CoV-2-specific IgG level decreases with time while IgA and a cellular response are maintained. IGRA proved to be a valuable test for the assessment of specific cellular immunity in immunocompromised HD patients and KTR.

scholarly journals Antibody and T Cell Response to SARS-CoV-2 Messenger RNA BNT162b2 Vaccine in Kidney Transplant Recipients and Hemodialysis Patients

2021 ◽  
pp. ASN.2021040480
Author(s):  
Dominique Bertrand ◽  
Mouad Hamzaoui ◽  
Veronique Lemée ◽  
Julie Lamulle ◽  
Melanie Hanoy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Kidney Transplant ◽  
Cell Response ◽  
Cellular Response ◽  
Hemodialysis Patients ◽  
T Cell Response ◽  
High Rate ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in patients with end stage renal disease and vaccination is hoped to prevent infection. Methods. Between January 18, and February 24, 2021, 225 kidney transplant recipients (KTR) and 45 hemodialysis patients (HDP) received two injections of mRNA BNT162b2 vaccine. The post-vaccinal humoral and cellular response was explored in the first 45 KTR and 10 HDP. Results. After the second dose, 8 HDP (88.9%) and 8 KTR (17.8%) developed anti-spike SARS-CoV-2 antibodies (p<0.0001). Median titer of antibodies in responders was 1052 AU/mL (IQR: 515-2689) in HDP and 671 AU/mL (IQR: 172-1523) in KTR (p=0.4). Nine HDP (100%) and 26 KTR (57.8%) showed a specific T cell response (p=0.06) after the second injection. In responders, median numbers of spike-reactive T cells were 305 SFC/106 CD3+ T cells (IQR: 95-947) in HDP and 212 SFC/106 CD3+ T cells (IQR: 61-330) in KTR (p=0.4). In KTR, the immune response to BNT162b2 seemed influenced by the immunosuppressive regimen, particularly tacrolimus or belatacept. Conclusion. Immunization with BNT162b2 seems more efficient in HDP, indicating that vaccination should be highly recommended in these patients awaiting a transplant. However, the current vaccinal strategy for KTR may not provide effective protection against COVID-19 and will likely need to be improved.

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