Generation of Aspergillus- and CMV- specific T-cell responses using autologous fast DC

Ramadan, Gamal; Konings, Steve; Kurup, Viswanath P.; Keever-Taylor, Carolyn A.

doi:10.1080/14653240410006040

Cited by 34 publications

(48 citation statements)

References 54 publications

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“…Based on these results, we prepared a series of 104 overlapping pentadecapeptides spanning the entire 427-aa coding region of Asp f16 and used a complete pentadecapeptide pool (Asp f16-PPC) pulsed onto dendritic cells (DC) to prime autologous proliferative and cytotoxic T lymphocyte (CTL) responses. For this purpose we used fast-DC derived from monocytes (Mo) in 2-3 days that were found previously by our laboratory to be as effective as standard-DC in the generation of Aspergillus -and CMV (cytomegalovirus)-specific T cell responses [21]. We found that Asp f16 is capable of inducing proliferative and cytotoxic Th1 T cell responses directed to a human leucocyte antigen (HLA) Class II restricted epitope from the Asp f16 allergen.…”

Section: I I Introductionmentioning

confidence: 99%

“…Most published studies designed to induce immune response to A. fumigatus , including our own [21], have used crude extracts from mycelia, spores and whole culture filtrates [18]. Such preparations contain, in addition to the relevant antigens, a large number of non-antigenic components including carbohydrates, proteins, nucleic acids and even toxins [22,23].…”

Section: I I Introductionmentioning

confidence: 99%

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

Ramadan

Davies

Kurup

et al. 2004

Clinical and Experimental Immunology

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Section: I I Introductionmentioning

confidence: 99%

Section: I I Introductionmentioning

confidence: 99%

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

Ramadan

Davies

Kurup

et al. 2004

Clinical and Experimental Immunology

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“…166,167 Similarly, DCs have been used in vaccines against fungal pathogens like aspergillosis 168 and may hold promise in priming pathogen-specific CTLs. 169,170 Like DCs and T-lymphocytes, NK cells mediate antitumor and anti-microbial responses. 171,172 For example, NK cells have been shown Table 5 Clinical strategies for immune restoration during HSCT (references in text) to mediate GVL effects via recognition of HLA class I antigens on tumor cells, while decreasing incidence of GVHD in nonmyeloablative and haploidentical transplantation.…”

Section: Cellular Factorsmentioning

confidence: 99%

Immune restoration following hematopoietic stem cell transplantation: an evolving target

Auletta

Lazarus

2005

Bone Marrow Transplant

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Summary:Hematopoietic stem cell transplantation (HSCT) is the definitive cure for many malignant and nonmalignant diseases. However, delays in immune reconstitution (IR) following HSCT significantly limit the success of transplantation and increase the risk for infection and disease relapse in the transplant recipient. Therefore, ways to measure and to manipulate immune recovery following HSCT are emerging and their success depends directly upon an enhanced understanding for the underlying mechanisms responsible for reconstituted immunity and hematopoiesis. Recent discoveries in the activation, function, and regulation of dendritic cell (DC), natural killer (NK) cell, and T-lymphocyte subtypes have been critical in developing immunotherapies used to prevent graft-versushost disease and to enhance graft-versus-leukemia. For example, regulatory T cells that induce tolerance and NK receptor-tumor ligand disparities that result in tumor lysis are being used to minimize GVHD and tumor burden, respectively. Furthermore, expansion and modulation of immune effector cells are being used to augment hematopoietic and immune recovery and to decrease transplantrelated toxicity in the transplant recipient. Specifically, DC expansion and incorporation into antitumor and antimicrobial vaccines is fast approaching application into clinical trials. This paper will review our current understanding for IR following HSCT and the novel ways in which to restore immune function and decrease transplantrelated toxicity in the transplant recipient. Bone Marrow Transplantation (2005) 35, 835-857.

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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%

“…Unless otherwise indicated, monocyte-depleted peripheral blood lymphocytes were stimulated three times at 7-10 day intervals using immature DCs, as described previously (Ramadan et al, 2004), then subsequently stimulated with Ad PP-pulsed autologous BLCLs as (Zhu et al, 2007). Cultures were initiated in X-VIVO 15/5 % AB serum (BioWhittaker) and 500 pg IL-12 ml 21 , at a ratio of 1 : 10 DCs : T cells.…”

Section: Methodsmentioning

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 Aspergillus- and CMV- specific T-cell responses using autologous fast DC

Cited by 34 publications

References 54 publications

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

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

Immune restoration following hematopoietic stem cell transplantation: an evolving target

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

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