scholarly journals Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy

2021 ◽  
Author(s):  
Sachin P Gadani ◽  
Maria Reyes-Mantilla ◽  
Larissa Jank ◽  
Samantha Harris ◽  
Morgan Douglas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Immune Response ◽  
Ifn Gamma ◽  
Cell Responses ◽  
Anti Cd20 ◽  
Humoral Responses

Background: Sphingosine-1-phosphate receptor (S1P) modulators and antiCD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Whether disease modifying therapies (DMTs) for multiple sclerosis (MS) also impact T cell immune response to vaccination is unknown. Methods: In 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum. We also measured T cell responses using FluoroSpot assay for interferon gamma (IFN-gamma; Mabtech,Sweden) using cryopreserved rested PBMCs and then incubated in cRPMI with 1microg/ml of pooled peptides spanning the entire spike glycoprotein (Genscript, 2 pools; 158 peptides each). Plates were read on an AID iSpot Spectrum to determine number of spot forming cells (SFC)/10 6 PBMCs. We tested for differences in immune responses across DMTs using linear models. Findings: Humoral responses were detected in 22/39 (56.4%) participants on anti-CD20 and in 59/63 (93.6%) participants on no or other DMTs. In a subset with immune cell phenotyping (n=88; 87%), T cell responses were detected in 76/88 (86%), including 32/33 (96.9%) participants on anti-CD20 therapies. AntiCD20 therapies were associated with an increase in IFN-gamma; SFC counts relative to those on no DMT or other DMTs (for antiCD20 vs. no DMT: 425.9% higher [95%CI: 109.6%, 1206.6%] higher; p<0.001; for antiCD20 vs. other DMTs: 289.6% [95%CI: 85.9%, 716.6%] higher; p<0.001). Interpretation: We identified a robust T cell response in individuals on anti-CD20 therapies despite a reduced humoral response to SARS-CoV-2 vaccination. Follow up studies are needed to determine if this translates to protection against COVID-19 infection.

scholarly journals Comparative analysis of human immune responses following SARS-CoV-2 vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S

2021 ◽  
Author(s):  
Dominique J. Barbeau ◽  
Judith M. Martin ◽  
Emily Carney ◽  
Emily Dougherty ◽  
Joshua D. Doyle ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cell Response ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
T Cell Response ◽  
Virus Neutralization ◽  
Cell Responses ◽  
Humoral Responses ◽  
Prospective Longitudinal

AbstractBackgroundThree SARS-CoV-2 vaccines, two based on mRNA, BNT162b2 and mRNA-1273, and one based on an adenovirus platform, Ad26.COV2.S, received emergency use authorization by the U.S. Food and Drug Administration in 2020/2021. These vaccines displayed clinical efficacy in initial studies against confirmed COVID-19 of 95.0%, 94.1%, and 66.9%, respectively.MethodsIndividuals receiving one of these vaccines were invited to participate in a prospective longitudinal comparative study of immune responses elicited by the three vaccines. In this observational cohort study, humoral responses were evaluated using a SARS-CoV-2 receptor-binding domain (RBD) ELISA and a SARS-CoV-2 virus neutralization assay at mean of 21-31 days and 45-63 days following each initial vaccination. IFN-γ ELISPOT assays were conducted with peripheral blood mononuclear cells obtained at a median of 45-63 days after each initial vaccination.ResultsThe two mRNA-based platforms elicited similar RBD ELISA responses and neutralizing antibody responses. The adenovirus-based vaccine elicited significantly lower RBD ELISA and SARS-CoV-2 virus neutralization activity. The mRNA-1273 vaccine elicited significantly higher spike glycoprotein-specific T cell responses than either the BNT162b2 or the Ad26.COV2.S vaccines.ConclusionsBoth mRNA based vaccines elicited higher magnitude humoral responses than Ad26.COV2.S and mRNA1273 elicited the highest magnitude of T cell response. Neutralizing antibody titers correlated with reported estimates of vaccine efficacy.Summary of key pointsWe compared antigen specific humoral and T cell responses following vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. Both mRNA based vaccines elicited higher magnitude humoral responses than Ad26.COV2.S and mRNA1273 elicited the highest magnitude of T cell response.

scholarly journals Patients treated with anti-CD20 therapy can mount robust T cell responses to mRNA-based COVID-19 vaccines

2021 ◽  
Author(s):  
Madelon Natacha ◽  
Kim Lauper ◽  
Gautier Breville ◽  
Irène Sabater Royo ◽  
Rachel Goldstein ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Rheumatic Diseases ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Specific Antibodies ◽  
Cell Responses ◽  
Anti Cd20 ◽  
Humoral Responses

Patients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. This study assesses humoral and T-cell responses to mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8+ T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). Vaccine-specific CD4+ and CD8+ T cells were polyfunctional but expressed more IL-2 in patients than in controls. In summary, our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the prevention of severe COVID-19.

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.

T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

1996 ◽  
Vol 1 (5) ◽  
pp. 270-278 ◽  
Author(s):  
CM Pelfrey ◽  
LR Tranquill ◽  
AB Vogt ◽  
HF McFarland
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Demyelinating Disease ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
T Cell Response ◽  
Healthy Controls ◽  
Cell Responses ◽  
Hla Binding ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which autoimmune T lymphocytes reacting with myelin antigens are believed to play a pathogenic role. Since HLA binding is involved in the selection of T cell responses, we have examined PLP peptide binding to HLA DR2, an HLA allele frequently found in MS patients. Both PLP 40–60 and PLP 89–106 show significant, high affinity binding to HLA DR2. We then tested whether responses to PLP peptides 40–60 and 89–106 are elevated in multiple sclerosis patients compared to matched controls. We also analysed T cell responses to MBP 87–106, which is considered to be the immunodominant region of MBP in humans. Here we demonstrate heterogenous T cell responses to PLP 40–60, PLP 89–106 and MBP 87–106 in both MS patients and controls. The overall number of TCL and the HLA restriction of those TCL did not vary significantly in the two groups. PLP 40–60 specific cytolytic TCL were increased in MS patients, whereas healthy controls had increased percentages of cytolytic TCL responding to PLP 89–106 and MBP 87–106. Although the data presented here shows heterogenous responses in T cell numbers, differences in numbers and specificity of cytolytic cells could be involved in the pathogenesis of autoimmune demyelinating disease.

scholarly journals Potent HIV-1-Specific CD8 T Cell Responses Induced in Mice after Priming with a Multiepitopic DNA-TMEP and Boosting with the HIV Vaccine MVA-B

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 424 ◽  
Author(s):  
Beatriz Perdiguero ◽  
Suresh C. Raman ◽  
Cristina Sánchez-Corzo ◽  
Carlos Oscar S. Sorzano ◽  
José Ramón Valverde ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Hiv 1

An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the best solution to provide a sustainable control and/or eradication of the virus. We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and therapeutic clinical trials, but was unable to prevent viral rebound after antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we described the design and immune responses elicited in mice by a new T cell multi-epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous or heterologous prime/boost regimens in combination with MVA-B. The TMEP-B protein contained conserved regions from Gag, Pol, and Nef proteins including multiple CD4 and CD8 T cell epitopes functionally associated with HIV control. Heterologous DNA-TMEP/MVA-B regimen induced higher HIV-1-specific CD8 T cell responses with broader epitope recognition and higher polyfunctional profile than the homologous DNA-TMEP/DNA-TMEP or the heterologous DNA-GPN/MVA-B combinations. Moreover, higher HIV-1-specific CD4 and Tfh immune responses were also detected using this regimen. After MVA-B boost, the magnitude of the anti-VACV CD8 T cell response was significantly compromised in DNA-TMEP-primed animals. Our results revealed the immunological potential of DNA-TMEP prime/MVA-B boost regimen and supported the application of these combined vectors in HIV-1 prevention and/or therapy.

scholarly journals Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Bobby Brooke Herrera ◽  
Wen-Yang Tsai ◽  
Charlotte A. Chang ◽  
Donald J. Hamel ◽  
Wei-Kung Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Vaccine Development ◽  
T Cell Responses ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses

ABSTRACT Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses. IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.

EBV-positive lymphoma patients have a selective deficiency in EBV immunity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21032-21032
Author(s):  
K. N. Heller ◽  
P. G. Steinherz ◽  
C. S. Portlock ◽  
C. Münz
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Specific Immune Response ◽  
Cell Responses

21032 Background: Epstein-Barr virus (EBV) asymptomatically establishes persistent infections in more than 90% of the adult population. However, due to effective immune control, only a minority of infected carriers develops spontaneous EBV-associated lymphomas. Since EBV nuclear antigen-1 (EBNA1) is the only protein expressed in all proliferating EBV infected cells we hypothesize that EBNA1 specific immune response is critical in preventing EBV-positive lymphomas. Methods: After informed consent, peripheral blood from healthy volunteers and lymphoma patients (prior to therapy- no evidence of cytopenia) were stimulated (ex vivo) with overlapping peptides covering the immunogenic EBNA1 (aa400–641) sequence. Frequency of EBNA1-specific T-cells were assessed by intracellular cytokine staining and flow cytometric proliferation assays. Cytokine pattern, surface marker phenotype and functional reactivity against EBV specific and control antigens were analyzed. Results: Patient and volunteer immune responses to control antigens and other viruses were assessed and statistically indistinguishable. EBNA1 specific CD4+ T cell responses were detected among 18 of 20 healthy carriers, and among 10 of 16 patients with EBV-negative lymphoma (relative to healthy volunteers p=0.145 via paired student T test). None of the patients with EBV-positive lymphomas (n=8) had a detectable EBNA1-specific CD4+ T-cell response (p<0.003 relative to healthy volunteers and patients with EBV-negative lymphomas). Conclusions: Healthy volunteers and patients with EBV-negative lymphoma have statistically similar EBNA1-specific CD4+ T cell responses. Although patients with EBV-positive lymphoma have intact immune responses to common viruses and antigens, they selectively lack an EBNA1-specific CD4+ T cell response. An intact EBNA1 specific immune response among patients with EBV-negaitve lymphoma implies that lymphoma is not a cause of a selective immune deficiency. On the contrary, these findings suggest that EBNA1-specific CD4+ T cells are critical in the prevention of EBV mediated lymphomas, and a defect in EBNA1 specific immunity may leave EBV carriers suseptible to EBV-positive lymphomas. EBNA1- specific CD4+ T cell function may be a new target for therapies of EBV-associated malignancies. No significant financial relationships to disclose.

Allogeneic partially HLA-matched dendritic cells (DC) as a vaccine in metastatic renal cell cancer (mRCC): Final analysis of a clinical phase I/II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15053-e15053 ◽  
Author(s):  
Anne Flörcken ◽  
Joachim Kopp ◽  
Kamran Movassaghi ◽  
Antje van Lessen ◽  
Anna Takvorian ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Clinical Response ◽  
Cell Cancer ◽  
T Cell Responses ◽  
T Cell Response ◽  
Delayed Type Hypersensitivity ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Cell Responses

e15053 Background: Despite novel kinase inhibitors, prognosis of metastatic RCC remains poor and new experimental approaches are warranted. Our aim was to evaluate a DC-based vaccine, which exploits alloreactivity as a means to amplify specific anti-tumor immune responses. Methods: Allogeneic, partially HLA-matched DC were generated in our GMP facility. DC were loaded with autologous tumor lysate. 8 patients with progressive mRCC were included, 7 patients were immunized repetitively with 107 DC s.c. over 20 weeks. Low-dose IL-2 (3 Mio U s.c. qd) was used concomitantly. Endpoints of the study were feasibility, safety, immunological and clinical responses. T cell responses against HLA-A2-restricted RCC-associated antigens were evaluated by proliferation assays, ELISpot and cytokine bead array (CBA). T cell repertoire was analysed by T cell receptor γ and –β PCR. Results: Vaccination was feasible and safe, no treatment-related grade 3/4 toxicity or clinically relevant autoimmunity was observed. No objective responses were observed, however, 2/7 patients showed stable disease, one a minimal clinical response. The mean TTP was 24.6 weeks (range 5 to 96). Delayed-type hypersensitivity was detected in 3/7 and HLA antibodies were induced in 3/7 patients. In 3/7 patients T cell responses against RCC-associated antigens such as TYMS, G250, vimentin, surviving and cyclin-D1 were induced by vaccination. These antigen-specific T cells showed a predominant TH1-cytokine profile. Interestingly, a clonally expanded T cell population could be detected by γ- and –β PCR in one patient with both a minimal clinical response and a T cell response. This clone is currently persisting for more than 80 months, its specificity is under investigation. Conclusions: Vaccination with allogeneic tumor-lysate-loaded DC was feasible, safe and was able to induce TH1-polarized immune responses against RCC-associated antigens. Tumor vaccination might be a promising approach in minimal residual disease, possibly in combination with antibodies against CTLA-4 or PD-1.

scholarly journals Immune Responses in Perforin Deficient Mice

2021 ◽  
Author(s):  
◽  
Helen Mary Alys Simkins
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Influenza Infection ◽  
T Cell Responses ◽  
Nkt Cells ◽  
T Cell Response ◽  
Dependent Manner ◽  
Cell Responses

<p>Dendritic cells (DC) play a pivotal role in the initiation of T cell responses and earlier studies have shown that their survival is important for the generation of effective immune responses. Cytotoxic T lymphocytes (CTL) and natural killer T (NKT) cells have been proposed to regulate the survival of antigen presenting DC through their ability to kill cells expressing specific antigen via secretion of perforin, a protein contained in cytotoxic granules. Perforin knockout (PKO) mice generate amplified immune responses to DC immunization, suggesting a link between defective cytotoxicity and increased T cell responses. The studies in this thesis used PKO mice and in vivo models of CD8+T cells and NKT cell immune responses to determine whether CTL and NKT cells eliminate DC in a perforin-dependent manner, and whether DC elimination is a mechanism to regulate T cell responses. During a primary influenza infection C57BL/6 and PKO mice generated a similar influenza specific CD8+ immune response. No significant difference in the percentage of influenza epitope PA224-233 specific T cells was observed between C57BL/6 and PKO mice during a secondary influenza infection, but PKO mice had a significantly reduced T cell response directed towards the dominant influenza epitope, NP366-374. The reduced T cell response in PKO mice was not due to differences in activation or differentiation status of specific T cells compared to C57BL/6 mice. Therefore, the extended DC survival in PKO after secondary influenza viral infection, recently reported by other authors, does not appear to correlate with increased expansion of virus specific CD8+T cells in infected mice. The role of NKT cells in DC elimination was assessed in vivo using the NKT cell ligand a-Galactosylceramide (a-GalCer). Injection of a-GalCer in C57BL/6 mice induced a dramatic decline in the number of splenic CD8+DC. A similar decrease in CD8+DC numbers was observed in PKO mice, suggesting that the mechanism of DC loss did not involve perforinmediated killing. In contrast, treatment with a TNF-a neutralizing antibody substantially reduced the decline in CD8+DC numbers. This reduction in splenic CD8+DC occurred as early as 15 hr after a-GalCer treatment, and did not affect generation of CD8+T cell responses or the ability of a-GalCer treatment to provide tumour protection. Taken together, these results suggest that multiple cells and mechanisms can regulate DC survival in vivo. CTL regulate DC survival in vivo in a perforin-dependent manner, but this does not necessarily affect the magnitude of the resulting immune responses. NKT cells also affect the survival of DC in vivo, but in a perforin-independent, cytokine-dependent manner. These findings provide additional knowledge about the in vivo involvement of perforin in regulating DC survival by CTL and NKT cells and the effects this has on T cell responses.</p>

Sign in / Sign up

Export Citation Format

Share Document