Characterization of the Cellular Immune Responses to Rhizopus oryzae and Impact on Immunotherapeutic Strategies in Hematopoietic Stem Cell Transplantation

Ref ID: 18722

Author:

T. Lehrnbecher, MD – Professor1, L. Tramsen, MD – Physician 1, S. Perkhofer, PhD – Professor 2, C. Lass-Flörl, MD, PhD – Professor 3, F. Roeger, none – Research Assistant 1, R. Schubert, PhD – Professor 1, S. Schmidt, PhD – Fellow 1;

Author address:

1Johann Wolfgang Goethe-Univ., Frankfurt, Germany, 23fhg-Univ. of Applied Sci. Tyrol, Innsbruck, Austria, 32Dept. of Hygiene, Microbiol., and Social Med., Univ. of Innsbruck, Innsbruck, Austria.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Infections due to Mucormycetes are increasingly reported and have a poor outcome, in particular in allogeneic hematopoietic stem cell transplantation (HSCT). Whereas adoptive immunotherapy transferring donor-derived anti-Aspergillus TH1 cells has been shown to be beneficial in HSCT recipients suffering from invasive aspergillosis, little is known about the cellular immunity against Mucormycetes. Methods: A total of 1×108 peripheral blood mononuclear cells from healthy volunteers were incubated overnight with antigens of Rhizopus oryzae. Stimulated cells were enriched by means of CD154 and interferon (IFN)-γ selection. After further expansion, cells were phenotypically and functionally characterized by flow-cytometry. Results: In all six individual tested, isolated and cultivated cells were characterized as a highly homogenous population of CD4+ T-cells which expressed HLA-DR and CD45RO, but lost CD62L, indicating an activated effector/memory T-helper cell population. Upon restimulation, the cells produced IFN-γ and TNF-α , but no IL-4 or IL-10, indicating a TH1 population. The generated cells were able to proliferate upon restimulation and showed cross-reactivity to other Mucormycetes (e.g., Rhizopus microsporus, Rhizomucor pusillus, and Mucor circinelloides). In addition, the generated cells exhibited a lower alloreactive potential compared to the original cell fraction, and increased the phagocyte activity of granulocytes and monocytes. Conclusions: Our data suggest that donor-derived anti-R. oryzae TH1 cells might be a potential tool for adoptive immunotherapy in allogeneic HSCT recipients suffering from mucormycosis.

Abstract Number: M-1708

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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