Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individuals and patients with hematologic malignancies.
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 gamma (IFN-gamma) in culture supernatants on stimulation with A fumigatus antigens was demonstrated in 13 of 17 healthy individuals, indicating a T(H)1 response. In patients with clinical evidence of invasive aspergillosis, a favorable response to antifungal therapy was found to correlate with a higher IFN-gamma/interleukin 10 (IL-10) ratio in culture supernatants (n = 7; median ratio, IFN-gamma/IL-10 = 1.0; range, 0.09-24.8) compared to 10 patients with progressive or stable disease (median ratio, IFN-gamma/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-gamma 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-gamma/IL-10 ratio. In addition, phosphoantigen-reactive V(gamma)9/V(delta)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.
Hebart
Holger
H
Department of Hematology and Oncology, Institute for Medical Information Processing, Eberhard-Karls-Universität Tübingen, Tübingen, Germany. hrhebart@med.uni-tuebingen.de
Bollinger
Claudia
C
Fisch
Paul
P
Sarfati
Jacqueline
J
Meisner
Christoph
C
Baur
Manuela
M
Loeffler
Jürgen
J
Monod
Michel
M
Latgé
Jean-Paul
JP
Einsele
Hermann
H
D000293:Adolescent; D000328:Adult; D000946:Antigens, Fungal / Q000276:immunology*; D001228:Aspergillosis / Q000150:complications / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D002374:Catalase / Q000276:immunology*; D002457:Cell Extracts / Q000276:immunology; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D005656:Fungal Proteins / Q000276:immunology; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000150:complications / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008172:Lung Diseases, Fungal / Q000150:complications / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000946:Antigens, Fungal; D002457:Cell Extracts; D005656:Fungal Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D002374:Catalase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C470567:dipeptidylpeptidase V, Asperigillus fumigatus