Human TCRαβ(+) CD4(-)CD8(-) double-negative (DN) T cells represent a minor subset in peripheral blood, yet are important in infectious diseases and autoimmune responses. We examined the frequency of DN T cells in 17 patients after allogeneic hematopoietic stem cell transplantation (aHSCT) at 1, 2, 3, 6, and 12 months post-aHSCT and show that these cells increase early after aHSCT and decrease with time after aHSCT. DN T cells reside in the terminally differentiated effector (CD45RA(+)CCR7(-)) T-cell population and are polyclonal, determined by T-cell receptor Vβ CDR3 analysis.
View Article and Find Full Text PDFBackground: Novel treatment options are urgently needed for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, which are associated with immune dysfunction and poor treatment outcomes. Mesenchymal stromal cells (MSCs) are immunomodulatory and adjunct autologous treatment with bone marrow-derived MSCs might improve clinical outcome by transforming chronic inflammation into productive immune responses. Our aim was to assess the safety of infusion of autologous MSCs as an adjunct treatment in patients with tuberculosis.
View Article and Find Full Text PDFBackground: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates.
Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M.
To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that triggers potent and long-lived immunity is urgently required. A plasmid-based vaccine has been developed to enhance activation of major histocompatibility complex (MHC) class I-restricted CD8⁺ cytolytic T cells using a recombinant Bacille Calmette-Guérin (rBCG) expressing a pore-forming toxin and the Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the same Mtb antigens.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug resistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of biomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the development of improved TB vaccines.
Methods: Recombinant proteins (n = 7) and peptide pools (n = 14) from M.
High-tuberculosis (TB)-burden countries are located in sub-Saharan Africa. We examined the frequency of human leukocyte antigen (HLA) alleles, followed by recombinant expression of the most frequent HLA-A alleles, i.e.
View Article and Find Full Text PDFIdentification of epitopes defined by T-cell responses aids to (1) monitor antigen-specific cellular immune responses (2) guide rational vaccine design, and (3) understand the nature of protective or harmful T-cell responses in diseases with defined target antigens. The 6-h intracellular cytokine staining (ICS) assay preferentially identifies effector T cells that are readily detectable in the peripheral circulation. In contrast, the whole blood assay (WBA) allows to gauge expansion of antigen-specific T cells over time (7 days), i.
View Article and Find Full Text PDFBackground: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing perfringolysin (in 6 animals) followed by two boosts (delivered intramuscullary) with non-replicating adenovirus 35 (rAd35) expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta).
View Article and Find Full Text PDFInnate immunity represents the first line of defence to pathogens besides the physical barrier and seems to play a role in protection against HIV/SIV infection and disease progression. High production of beta-chemokines and CD8+ T cell anti-viral factors in naive as well as in vaccinated macaques has been associated with complete or partial protection against SIV infection indicating that genetic or environmental factors may influence their production. This innate immunity may help in generating HIV/SIV-specific responses upon the first exposure to HIV/SIV.
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