Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from the<i>Aspergillus</i>f16 allergen

Ramadan, Gamal; Davies, B.; Kurup, Viswanath P.; Keever-Taylor, Carolyn A.

doi:10.1111/j.1365-2249.2005.02699.x

Cited by 35 publications

(37 citation statements)

References 55 publications

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“…12 In contrast to the generation of virus-specific T cells, such as T cells specific for CMV, Epstein-Barr virus (EBV), or adenovirus, [13][14][15] few data exist regarding functionally active anti-Aspergillus T cells. 10,[16][17][18] In addition, most of the approaches to generate antigen-specific T cells using peptide-pulsed dendritic cells (DCs) 16,19 and antigenpulsed DCs 20,21 or genetically modified antigen-presenting cells (APCs) 22 are labor intensive and require several weeks for the generation of a clinical product.…”

Section: Introductionmentioning

confidence: 99%

Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus

Beck

Topp

Koehl

et al. 2006

Blood

118

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Invasive aspergillosis remains a serious complication in patients undergoing allogeneic stem cell transplantation (SCT). Since it became clear that lymphocytes provide a critical secondary defense against fungi, adoptive transfer of functionally active anti-Aspergillus T cells might be an option to restore adaptive immune effector mechanisms. Using the interferon (IFN)-␥ secretion assay, we isolated human activated T cells upon stimulation with a cellular extract of Aspergillus fumigatus. Culturing this cell population for 14 days, we obtained an average of 1.1 ؋ 10 7 cells from a single 100-mL blood draw in 7 of 7 healthy individuals. Within another 14 days, these cells were expanded to an average number of 2.0 ؋ 10 8 T-helper 1 (T H 1) cells secreting IFN-␥ on stimulation with Aspergillus antigens. Testing various fungal antigen extracts, similar proportions of IFN-␥-producing CD3 ؉ /CD4 ؉ cells were obtained upon activation with antigen extracts of A fumigatus, A flavus, A niger, and Penicillium chrysogenum, whereas no significant IFN-␥ production was observed upon activation with antigen extracts of Alternaria alternata and Candida albicans. In addition, generated T cells were able to induce damage to A fumigatus hyphae, and significantly increased hyphal damage induced by human neutrophils. CD4 ؉ T-cell-mediated alloreactivity of generated anti-Aspergillus T cells was clearly reduced compared with that of the original cell population. In conclusion, we present a simple and feasible strategy for rapid generation of a high number of functional active T cells against Aspergillus from a single blood draw. Our data suggest that functionally active T cells against Aspergillus could be a promising treatment option for patients undergoing allogeneic SCT. IntroductionInvasive aspergillosis (IA) remains a major cause of morbidity and mortality in patients with hematologic malignancies, particularly in patients who have undergone allogeneic stem cell transplantation (SCT). 1 Important risk factors for IA are neutropenia and defects in the phagocyte cell function. 2 On the other hand, there is an increasing body of evidence that adaptive immune response also plays a critical role in the host defense against Aspergillus fumigatus, the most frequent cause of IA. For example, IA has been reported with increasing frequency in patients with advanced AIDS, 3 and up to two-thirds of patients with IA diagnosed after allogeneic SCT are not neutropenic. 1 In contrast to neutrophil recovery, which generally occurs within the first 2 to 3 weeks after SCT, the number of functional T cells and T-cell function increase slowly over the first few months after transplantation. 4 Prolonged immune suppression due either to transplant conditioning and graft-versus-host disease (GVHD) prophylaxis or to treatment of GVHD further increase the risk of IA in SCT patients. 5,6 It has recently been shown that a significant antigen-specific proliferation of interferon (IFN)-␥-producing T cells occurred in healthy individuals and in patients survi...

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Section: Introductionmentioning

confidence: 99%

Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus

Beck

Topp

Koehl

et al. 2006

Blood

118

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“…6 In healthy individuals the presence of Aspergillus-specific T cells in peripheral blood was demonstrated by stimulating peripheral blood mononuclear cells (PBMC) with Aspergillus crude extracts or conidia, A. fumigatus recombinant proteins or overlapping peptides of A. fumigatus proteins. 5,[7][8][9][10][11][12][13] We have previously identified Crf1-and Catalase1-specific T cells in healthy individuals using overlapping peptides. Crf1-and Catalase1-specific T cells recognizing a broad variety of T-cell epitopes were identified in the majority of healthy individuals and Aspergillus reactivity was shown by stimulating the T cells with Aspergillus protein extract or recombinant protein.…”

Section: Introductionmentioning

confidence: 99%

Induction of A. fumigatus-specific CD4-positive T cells in patients recovering from invasive aspergillosis

et al. 2014

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ABSTRACTmade at the Leiden University Medical Center (LUMC, Leiden, The Netherlands). For the production of Catalase1 recombinant protein, three Catalase1 fragments were generated with a 12-amino acid overlap. We used the A. fumigatus strain CBS144.89 for the in-house preparation of Aspergillus crude extract. Commercially available crude extracts of strain CBS192.65 (HAL Allergy, Leiden, The Netherlands) and strain CBS545.65 (Allergon, Ängelholm, Sweden) were also used (see the Online Supplementary Methods for details).

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“…Similar to CMV (Trivedi et al, 2005) and Aspergillus (Ramadan et al, 2004(Ramadan et al, , 2005aZhu et al, 2007), the use of protein-spanning overlapping pools of pentadecapeptides proved highly effective at priming T-helper 1 cellular immune responses to targeted conserved regions of Ad hexon. Consistent with our experience with Aspergillus (Zhu et al, 2007), optimal results were obtained by switching to BLCLs as APCs after initial use of DCs.…”

Section: Discussionmentioning

confidence: 99%

Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived from conserved regions of the adenovirus hexon protein

Zhu¹,

Xu²,

Tsao³

et al. 2010

Journal of General Virology

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Many of the 51 serotypes of adenovirus have been associated with clinically relevant infection. Adenovirus can disseminate rapidly in patients with a compromised immune system, such as that which occurs secondary to haematopoietic progenitor-cell transplantation. The higher rate of infection in recipients of T cell-depleted grafts and in those undergoing T cell-targeted treatment during graft versus host disease demonstrates the importance of a T-cell response in preventing disseminated infection. Studies have shown that the memory response to adenovirus is directed primarily to the hexon protein and is dominated by CD4 + T cells, probably due to the ability of the virus to block its presentation on HLA class I antigens. We have developed an approach to expand adenovirus-specific T cells using a pool of overlapping pentadecapeptides derived from selected conserved regions of hexon. We characterized responses to identify the peptides that are recognized, the responding T-cell subsets and their HLA restriction. Of eight lines that were characterized extensively, seven included both CD4 + and CD8 + T cells and each recognized between two and eight unique peptide sequences. By focusing the response on the conserved sequences of hexon, the cell lines are likely to recognize most of the serotypes responsible for clinically relevant disease. The 15 aa peptides used to prime the responses are more likely than whole virus or longer peptides to expand the less frequent CD8 + memory subset. Lines prepared by using our method may be more effective in adoptive immunotherapy protocols designed to prevent or treat disseminated adenovirus infections in high-risk patients.

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Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from theAspergillusf16 allergen

Abstract: SummaryThe Aspergillus allergen Asp f16 has been shown to confer protective Th1 T cell-mediated immunity against infection with Aspergillus conidia in murine models. Here, we use overlapping (

Cited by 35 publications

References 55 publications

Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus

Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus

Induction of A. fumigatus-specific CD4-positive T cells in patients recovering from invasive aspergillosis

Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived from conserved regions of the adenovirus hexon protein

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