scholarly journals Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells

2003 ◽  
Vol 197 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Carlos Ocaña-Morgner ◽  
Maria M. Mota ◽  
Ana Rodriguez
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Blood Stage ◽  
Liver Stage ◽  
Cell Responses ◽  
Blood Stage Infection ◽  
Stage Infection

Malaria starts with Plasmodium sporozoites infection of the host's liver, where development into blood stage parasites occurs. It is not clear why natural infections do not induce protection against the initial liver stage and generate low CD8+ T cell responses. Using a rodent malaria model, we show that Plasmodium blood stage infection suppresses CD8+ T cell immune responses that were induced against the initial liver stage. Blood stage Plasmodium affects dendritic cell (DC) functions, inhibiting maturation and the capacity to initiate immune responses and inverting the interleukin (IL)-12/IL-10 secretion pattern. The interaction of blood stage parasites with DCs induces the secretion of soluble factors that inhibit the activation of CD8+ T cells in vitro and the suppression of protective CD8+ T cell responses against the liver stage in vivo. We propose that blood stage infection induces DCs to suppress CD8+ T cell responses in natural malaria infections. This evasion mechanism leaves the host unprotected against reinfection by inhibiting the immune response against the initial liver stage of the disease.

scholarly journals Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mauro Di Pilato ◽  
Miguel Palomino-Segura ◽  
Ernesto Mejías-Pérez ◽  
Carmen E. Gómez ◽  
Andrea Rubio-Ponce ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Adaptive Immune System ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Adaptive Immune

AbstractNeutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

Sipuleucel-T (sip-T)–induced proliferative CD8+ T-cell responses to immunizing and secondary antigens.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 165-165 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
David I. Quinn ◽  
Adam S. Kibel ◽  
Daniel Peter Petrylak ◽  
Nancy N. Chang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Antibody Responses ◽  
Castration Resistant Prostate Cancer ◽  
Peripheral Blood Mononuclear ◽  
Cell Responses

165 Background: Sip-T is an FDA-approved autologous immunotherapy for patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Sip-T is manufactured from peripheral blood mononuclear cells cultured with PA2024, a fusion antigen of prostatic acid phosphatase (PAP) conjugated to granulocyte macrophage-colony stimulating factor (GM-CSF). In sip-T–treated pts, T cell and antibody responses to PA2024 or PAP as well as antibody responses to secondary antigens (i.e., antigen spread) correlate with improved overall survival. To explore the biology of this relationship, we further characterized the T cell subpopulations involved in the cellular immune responses to sip-T. Methods: In vitro proliferative CD8+ (cytotoxic T lymphocyte) and CD4+ (T helper) T cell responses to PA2024 and PAP as well as to secondary antigens (PSA, LGALS3, and KRAS) were evaluated using flow cytometry on pt samples from two sip-T–containing clinical trials (STAND [NCT01431391] and STRIDE [NCT01981122]). Results: PA2024-specific CD8+ and CD4+ responses were observed beginning 2 weeks after the first sip-T infusion through week 26 in most evaluable pts. CD8+ and CD4+ responses to PAP were also observed, although the magnitude of this response (to a self-antigen) was smaller when compared with PA2024 responses. Most pts with CD8+ responses to PA2024 also had a CD4+ response, which occurred more frequently than CD8+ responses. Both CD8+ and CD4+ responses to secondary antigens were amplified after sip-T, and these CD8+ proliferative responses to secondary antigens were greater in magnitude compared with CD4+ responses. Conclusions: Here,we report the first evidence of antigen-specific CD8+ responses in pts receiving sip-T, indicating CD8+ T cell involvement in sip-T–mediated immune responses that occur in concert with the expected CD4+ T cell responses to soluble antigens (i.e., PA2024). These CD8+ responses were durable, lasting up to 26 weeks post–sip-T treatment. Importantly, responses to secondary antigens and in particular, CD8+ responses, were also amplified after sip-T treatment, suggesting that antigen spread could be resulting from sip-T–mediated tumor cell lysis. Clinical trial information: NCT01431391 and NCT01981122.

scholarly journals Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

2017 ◽  
Vol 214 (9) ◽  
pp. 2563-2572 ◽  
Author(s):  
Spencer W. Stonier ◽  
Andrew S. Herbert ◽  
Ana I. Kuehne ◽  
Ariel Sobarzo ◽  
Polina Habibulin ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Ebola Virus ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cd8 T Cell ◽  
Marburg Virus ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

scholarly journals Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Naïve Mice and Those with Preexisting Immunity

2011 ◽  
Vol 19 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Jin Huk Choi ◽  
Joe Dekker ◽  
Stephen C. Schafer ◽  
Jobby John ◽  
Craig E. Whitfill ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Transduction Efficiency ◽  
Virus Antibody ◽  
Cell Responses

ABSTRACTThe immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity.In vitroandin vivoassays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P= 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.

scholarly journals Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees.

2021 ◽  
Author(s):  
Alison Tarke ◽  
John Sidney ◽  
Nils Methot ◽  
Yun Zhang ◽  
Jennifer M Dan ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Comprehensive Analysis ◽  
T Cell Epitopes ◽  
Cell Reactivity ◽  
Cell Responses ◽  
Adaptive Immune ◽  
T Cell Reactivity

The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.

BK Polyomavirus–Specific CD8 T-Cell Expansion In Vitro Using 27mer Peptide Antigens for Developing Adoptive T-Cell Transfer and Vaccination

2020 ◽  
Author(s):  
Maud Wilhelm ◽  
Amandeep Kaur ◽  
Marion Wernli ◽  
Hans H Hirsch
Keyword(s):  
T Cells ◽  
T Cell ◽  
Kidney Transplant ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Bk Polyomavirus

Abstract Background BK polyomavirus (BKPyV) remains a significant cause of premature kidney transplant failure. In the absence of effective antivirals, current treatments rely on reducing immunosuppression to regain immune control over BKPyV replication. Increasing BKPyV-specific CD8 T cells correlate with clearance of BKPyV DNAemia in kidney transplant patients. We characterized a novel approach for expanding BKPyV-specific CD8 T cells in vitro using 27mer-long synthetic BKPyV peptides, different types of antigen-presenting cells, and CD4 T cells. Methods Langerhans cells and immature or mature monocyte-derived dendritic cells (Mo-DCs) were generated from peripheral blood mononuclear cells of healthy blood donors, pulsed with synthetic peptide pools consisting of 36 overlapping 27mers (27mP) or 180 15mers (15mP). BKPyV-specific CD8 T-cell responses were assessed by cytokine release assays using 15mP or immunodominant 9mers. Results BKPyV-specific CD8 T cells expanded using 27mP and required mature Mo-DCs (P = .0312) and CD4 T cells (P = .0156) for highest responses. The resulting BKPyV-specific CD8 T cells proliferated, secreted multiple cytokines including interferon γ and tumor necrosis factor α, and were functional (CD107a+/PD1–) and cytotoxic. Conclusions Synthetic 27mP permit expanding BKPyV-specific CD8 T-cell responses when pulsing mature Mo-DCs in presence of CD4 T cells, suggesting novel and safe approaches to vaccination and adoptive T-cell therapies for patients before and after kidney transplantation.

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 Persistent Recognition of Autologous Virus by High-Avidity CD8 T Cells in Chronic, Progressive Human Immunodeficiency Virus Type 1 Infection

2004 ◽  
Vol 78 (2) ◽  
pp. 630-641 ◽  
Author(s):  
R. Draenert ◽  
C. L. Verrill ◽  
Y. Tang ◽  
T. M. Allen ◽  
A. G. Wurcel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Gamma Interferon ◽  
High Avidity ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Stage Infection

ABSTRACT CD8 T-cell responses are thought to be crucial for control of viremia in human immunodeficiency virus (HIV) infection but ultimately fail to control viremia in most infected persons. Studies in acute infection have demonstrated strong CD8-mediated selection pressure and evolution of mutations conferring escape from recognition, but the ability of CD8 T-cell responses that persist in late-stage infection to recognize viruses present in vivo has not been determined. Therefore, we studied 24 subjects with advanced HIV disease (median viral load = 142,000 copies/ml; median CD4 count = 71/μl) and determined HIV-1-specific CD8 T-cell responses to all expressed viral proteins using overlapping peptides by gamma interferon Elispot assay. Chronic-stage virus was sequenced to evaluate autologous sequences within Gag epitopes, and functional avidity of detected responses was determined. In these subjects, the median number of epitopic regions targeted was 13 (range, 2 to 39) and the median cumulative magnitude of CD8 T-cell responses was 5,760 spot-forming cells/106 peripheral blood mononuclear cells (range, 185 to 24,700). On average six (range, one to 8) proteins were targeted. For 89% of evaluated CD8 T-cell responses, the autologous viral sequence was predicted to be well recognized by these responses and the majority of analyzed optimal epitopes were recognized with medium to high functional avidity by the contemporary CD8 T cells. Withdrawal of antigen by highly active antiretroviral therapy led to a significant decline both in breadth (P = 0.032) and magnitude (P = 0.0098) of these CD8 T-cell responses, providing further evidence that these responses had been driven by recognition of autologous virus. These results indicate that strong, broadly directed, and high-avidity gamma-interferon-positive CD8 T-cells directed at autologous virus persist in late disease stages, and the absence of mutations within viral epitopes indicates a lack of strong selection pressure mediated by these responses. These data imply functional impairment of CD8 T-cell responses in late-stage infection that may not be reflected by gamma interferon-based screening techniques.

Abstract B028: Blockade of the CD47 “Do not eat” signal by TTI-621 (SIRPαFc) leads to enhanced antitumor CD8+T cell responses in vitro

2016 ◽  
Author(s):  
Natasja Nielsen Viller ◽  
Tran Truong ◽  
Emma Linderoth ◽  
Lisa D. Johnson ◽  
Stephane Viau ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses
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