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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-01-0265.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4521-4528
IMMUNOBIOLOGY
Analysis of T-cell responses to Aspergillus
fumigatus antigens in healthy individuals and patients with
hematologic malignancies
Holger Hebart,
Claudia Bollinger,
Paul Fisch,
Jacqueline Sarfati,
Christoph Meisner,
Manuela Baur,
Jürgen Loeffler,
Michel Monod,
Jean-Paul Latgé, and
Hermann Einsele
From the Department of Hematology and Oncology,
Institute for Medical Information Processing,
Eberhard-Karls-Universität Tübingen, Tübingen,
Germany; Section of Molecular Pathology, Department of
Pathology, Albert-Ludwigs-Universität, Freiburg,
Germany; Institut Pasteur, Paris, France; and
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne,
Switzerland.
Invasive aspergillosis has become a major cause of
infection-related mortality in nonneutropenic patients after allogeneic stem cell transplantation (SCT). To assess the potential role of
Aspergillus-specific T-cell responses for the successful
control of invasive aspergillosis, lymphoproliferative responses to
Aspergillus fumigatus antigens were studied in
healthy individuals, patients with evidence of invasive aspergillosis,
and patients late after allogeneic SCT. In healthy individuals, a
positive lymphoproliferative response was documented to cellular
extracts of A fumigatus (14 of 16), the 88-kDa
dipeptidylpeptidase (4 of 16), and the 90-kDa catalase (8 of 11). A
predominant release of interferon  (IFN-) in culture supernatants
on stimulation with A fumigatus antigens was demonstrated
in 13 of 17 healthy individuals, indicating a TH1 response.
In patients with clinical evidence of invasive aspergillosis, a
favorable response to antifungal therapy was found to correlate with a
higher IFN-/interleukin 10 (IL-10) ratio in culture supernatants (n = 7; median ratio, IFN-/IL-10 = 1.0; range, 0.09-24.8)
compared to 10 patients with progressive or stable disease (median
ratio, IFN-/IL-10 = 0.1; range, 0.002-2.1; P = .04).
Steroid treatment was found to suppress
Aspergillus-specific lymphoproliferation (P = .037) and release of IFN- in culture supernatants
(P = .017). In contrast to cytomegalovirus- and tetanus
toxoid-specific T-cell responses, Aspergillus-specific
T-cell reconstitution late after allogeneic SCT was characterized by
low stimulation indices and a low IFN-/IL-10 ratio. In addition,
phosphoantigen-reactive V9/V 2 T-cell clones from healthy
individuals were found to produce significant amounts of tumor necrosis
factor in response to A fumigatus antigens. In conclusion,
these results further support the hypothesis that T cells contribute to
the host defense against A fumigatus.
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