The Innate Biologies of Adaptive Antigen Receptors

2020 ◽  
Vol 38 (1) ◽  
pp. 487-510 ◽  
Author(s):  
Adrian C. Hayday ◽  
Pierre Vantourout
Keyword(s):  
T Cell ◽  
Functional Outcomes ◽  
Germ Line ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Antigen Receptors ◽  
Adaptive Responses ◽  
Cell Responses ◽  
Somatic Recombination ◽  
Natural Killer Receptors

Nonclonal innate immune responses mediated by germ line–encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line–encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/β chains.

Impact of Immunosuppressive Drugs on Adaptive and Innate Immune Responses to Aspergillus fumigatus Antigens.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2222-2222
Author(s):  
Holger Hebart ◽  
Andreas Mickan ◽  
Ziad Haddad ◽  
Juergen Loeffler ◽  
Jean-Paul Latge ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Invasive Aspergillosis ◽  
Immunosuppressive Agents ◽  
T Cell Responses ◽  
Innate Immune ◽  
Strong Impact ◽  
Innate Immune Responses ◽  
Cell Responses ◽  
The Impact

Abstract Appropriate activation of the innate and adaptive immune system is crucial for the successful control of invasive aspergillosis (IA). Acute and chronic graft-versus-host disease as well as corticosteroids were described as major risk factors for the development of IA. In this study, we assessed the impact of immunosuppressive agents (dexamethasone, rapamycin, Cyclosporin A, FK506) on the A. fumigatus induced activation of monocyte-derived immature dendritic cells (iDC) and A. fumigatus-specific T-cell responses in well established cell culture models. Immature DCs were found to be activated and to differentiate into mature DCs in response to A. fumigatus antigens. The upregulation of CD86 was inhibited by dexamethasone (D) in 3 out of 3 experiments, and of CD40 and CD80 in 2/3. CSA and FK506 had a variable impact on the upregulation of CD86, but not on CD40 and CD80, whereas the expression of co-stimulatory molecules was found unchanged upon incubation with rapamycin. Autologous DCs were found to restore A. fumigatus-specific T-cell responses. T-cell proliferation to A. fumigatus hyphae and a cellular extract of the culture filtrate were found to be strongly inhibited by rapamycin and dexamethasone (n=3), whereas the effect of CSA and FK506 (n=3) at the concentrations analysed was variable. The release of IFN-g in culture supernatants upon stimulation with A. fumigatus antigens was strongly reduced in the presence of rapamycin (n=3), whereas the release of IL-4 was found to be increased in the majority of experiments (n=3). Comparable results were observed upon stimulation with tetanus toxoid and a CMV lysate (n=3). These data indicate, that A. fumigatus-spec. T-cell responses may be directed towards a TH2 phenotype in the presence of immunosuppressive agents. In summary, immunosuppressive agents were found to exert differential effects on adaptive and innate immune responses directed against A. fumigatus. Whereas dexamethasone was found to modulate the expression of co-stimulatory molecules on A. fumigatus activated iDCs and to suppress A. fumigatus-specific lymphoproliferation, rapamycin exerted only minor effects on DC-activation but had a strong impact on A. fumigatus-induced T-cell responses. These results may help to tailor immunosuppressive regimens in patients at high risk for invasive aspergillosis.

scholarly journals The Innate Immune Sensor NLRC3 Acts as a Rheostat that Fine-Tunes T Cell Responses in Infection and Autoimmunity

Immunity ◽  
2018 ◽  
Vol 49 (6) ◽  
pp. 1049-1061.e6 ◽  
Author(s):  
Toru Uchimura ◽  
Yoshitaka Oyama ◽  
Meng Deng ◽  
Haitao Guo ◽  
Justin E. Wilson ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Innate Immune ◽  
Cell Responses

scholarly journals Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses

Vaccines ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 4 ◽  
Author(s):  
Muktha S. Natrajan ◽  
Nadine Rouphael ◽  
Lilin Lai ◽  
Dmitri Kazmin ◽  
Travis L. Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Innate Immune ◽  
Antibody Responses ◽  
Cytokine Signaling ◽  
Cell Responses ◽  
Viral Vaccine ◽  
Tularemia Vaccine

Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed to characterize the innate and adaptive responses induced by two different lots of a live attenuated tularemia vaccine and compare them to other well-characterized viral vaccine immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) to determine changes in transcriptional activity that correlated with changes detected by cellular phenotyping, cytokine signaling, and serological assays. Transcriptional profiles after tularemia vaccination were compared with yellow fever [YF-17D], inactivated [TIV], and live attenuated [LAIV] influenza. Results: Tularemia vaccine lots produced strong innate immune responses by Day 2 after vaccination, with an increase in monocytes, NK cells, and cytokine signaling. T cell responses peaked at Day 14. Changes in gene expression, including upregulation of STAT1, GBP1, and IFIT2, predicted tularemia-specific antibody responses. Changes in CCL20 expression positively correlated with peak CD8+ T cell responses, but negatively correlated with peak CD4+ T cell activation. Tularemia vaccines elicited gene expression signatures similar to other replicating vaccines, inducing early upregulation of interferon-inducible genes. Conclusions: A systems vaccinology approach identified that tularemia vaccines induce a strong innate immune response early after vaccination, similar to the response seen after well-studied viral vaccines, and produce unique transcriptional signatures that are strongly correlated to the induction of T cell and antibody responses.

Structure-function relationships of chimeric antigen receptors in acute T cell responses to antigen

2020 ◽  
Vol 126 ◽  
pp. 56-64
Author(s):  
Han Xu ◽  
Agnes E. Hamburger ◽  
Jee-Young Mock ◽  
Xueyin Wang ◽  
Aaron D. Martin ◽  
...  
Keyword(s):  
T Cell ◽  
Structure Function ◽  
T Cell Responses ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Cell Responses

scholarly journals The Effects of Trained Innate Immunity on T Cell Responses; Clinical Implications and Knowledge Gaps for Future Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Dearbhla M. Murphy ◽  
Kingston H. G. Mills ◽  
Sharee A. Basdeo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cells ◽  
T Cell Responses ◽  
Innate Immune ◽  
Metabolic Reprogramming ◽  
Innate Immune Cells ◽  
Peripheral Tissues ◽  
Trained Immunity ◽  
Cell Responses

The burgeoning field of innate immune training, also called trained immunity, has given immunologists new insights into the role of innate responses in protection against infection and in modulating inflammation. Moreover, it has led to a paradigm shift in the way we think about immune memory and the interplay between innate and adaptive immune systems in conferring immunity against pathogens. Trained immunity is the term used to describe the medium-term epigenetic and metabolic reprogramming of innate immune cells in peripheral tissues or in the bone marrow stem cell niche. It is elicited by an initial challenge, followed by a significant period of rest that results in an altered response to a subsequent, unrelated challenge. Trained immunity can be associated with increased production of proinflammatory mediators, such as IL-1β, TNF and IL-6, and increased expression of markers on innate immune cells associated with antigen presentation to T cells. The microenvironment created by trained innate immune cells during the secondary challenge may have profound effects on T cell responses, such as altering the differentiation, polarisation and function of T cell subtypes, including Th17 cells. In addition, the Th1 cytokine IFN-γ plays a critical role in establishing trained immunity. In this review, we discuss the evidence that trained immunity impacts on or can be impacted by T cells. Understanding the interplay between innate immune training and how it effects adaptive immunity will give insights into how this phenomenon may affect the development or progression of disease and how it could be exploited for therapeutic interventions or to enhance vaccine efficacy.

scholarly journals Decoding the role of CBLB for innate immune responses regulating systemic dissemination during Non-Tuberculous Mycobacteria infection

2020 ◽  
Author(s):  
Srinivasu Mudalagiriyappa ◽  
Jaishree Sharma ◽  
Hazem F. M. Abdelaal ◽  
Thomas C. Kelly ◽  
Woosuk Choi ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Granulomatous Inflammation ◽  
Innate Immune ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Inflammatory Monocytes ◽  
Cell Immunity

AbstractNon-Tuberculous Mycobacteria (NTM) are ubiquitous in nature, present in soil and water, and cause primary leading to disseminated infections in immunocompromised individuals. NTM infections are surging in recent years due to an increase in an immune-suppressed population, medical interventions, and patients with underlying lung diseases. Host regulators of innate immune responses, frontiers for controlling infections and dissemination, are poorly defined during NTM infections. Here, we describe the role of CBLB, an E3-ubiquitin ligase, for innate immune responses and disease progression in a mouse model of NTM infection under compromised T-cell immunity. We found that CBLB thwarted NTM growth and dissemination in a time- and infection route- dependent manner. Mechanistically, we uncovered defects in many innate immune cells in the absence of Cblb, including poor responses of NK cells, inflammatory monocytes, and conventional dendritic cells. Strikingly, Cblb-deficient macrophages were competent to control NTM growth in vitro. Histopathology suggested the lack of early formation of granulomatous inflammation in the absence of CBLB. Collectively, CBLB is essential to mount productive innate immune responses and help prevent the dissemination during an NTM infection under T-cell deficiency.

scholarly journals Innate immune signatures to a partially-efficacious HIV vaccine predict correlates of HIV-1 infection risk

2021 ◽  
Vol 17 (3) ◽  
pp. e1009363
Author(s):  
Erica Andersen-Nissen ◽  
Andrew Fiore-Gartland ◽  
Lamar Ballweber Fleming ◽  
Lindsay N. Carpp ◽  
Anneta F. Naidoo ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Innate Immune ◽  
Cd4 T Cell ◽  
Type I ◽  
Transcriptional Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Immune Biomarkers ◽  
Hiv 1

The pox-protein regimen tested in the RV144 trial is the only vaccine strategy demonstrated to prevent HIV-1 infection. Subsequent analyses identified antibody and cellular immune responses as correlates of risk (CoRs) for HIV infection. Early predictors of these CoRs could provide insight into vaccine-induced protection and guide efforts to enhance vaccine efficacy. Using specimens from a phase 1b trial of the RV144 regimen in HIV-1-uninfected South Africans (HVTN 097), we profiled innate responses to the first ALVAC-HIV immunization. PBMC transcriptional responses peaked 1 day post-vaccination. Type I and II interferon signaling pathways were activated, as were innate pathways critical for adaptive immune priming. We then identified two innate immune transcriptional signatures strongly associated with adaptive immune CoR after completion of the 4-dose regimen. Day 1 signatures were positively associated with antibody-dependent cellular cytotoxicity and phagocytosis activity at Month 6.5. Conversely, a signature present on Days 3 and 7 was inversely associated with Env-specific CD4+ T cell responses at Months 6.5 and 12; rapid resolution of this signature was associated with higher Env-specific CD4+ T-cell responses. These are the first-reported early immune biomarkers of vaccine-induced responses associated with HIV-1 acquisition risk in humans and suggest hypotheses to improve HIV-1 vaccine regimens.

Sign in / Sign up

Export Citation Format

Share Document