Effects of interferon-alpha on cytokine profile, T cell receptor repertoire and peptide reactivity of human allergen-specific T cells.
A large panel of T cell clones (TCC) specific for the recombinant form of Poa pratensis allergen (rKBG7.2 or Poa p9) were established from the peripheral blood of grass pollen-sensitive donor in the absence or presence of recombinant interferon-alpha (IFN-alpha) in bulk culture and their pattern of cytokine secretion, peptide reactivity and TCR V beta repertoire was examined. The majority of allergen-specific TCC derived in absence of IFN-alpha produced high amounts of interleukin-4 (IL-4) and IL-5 but not IFN-gamma (Th2 cells), while most of TCC derived in presence of IFN-alpha produced IFN-gamma but not, or limited amounts of, IL-4 and IL-5 (Th1 or Th0 cells). Of 24 TCC established in the presence of IFN-alpha, 22 were able to recognize a single allergen peptide, p26, while none of the clones established in the absence of IFN-alpha showed a similar specificity. The majority of both clones expressed the V beta 2 element regardless of whether they were established in the presence of INF-alpha, but the presence of IFN-alpha favored the expansion of V beta 2+, V beta 17+ and V beta 22+ Poa p9-specific T cells, whereas in the absence of IFN-alpha, other TCR V beta-bearing T cells (V beta 5, and V beta 6.7, and V beta 14) were expanded in addition to V beta 2+ T cells. None of V beta 2+ clones established in the absence of IFN-alpha reacted with p26, whereas all the V beta 2+ clones established in its presence in the absence of interferon-alpha reacted with p26, whereas all the V beta 2+ clones established in its presence reacted to this peptide. IFN-alpha also shifted the TCR V beta repertoire of both Poa p9- and Lolium perenne group 1 (Lol p1)-specific T cell lines generated from the same patient and from a different grass-sensitive individual. These data demonstrate that IFN-alpha modulates the development of allergen-specific T cells in vitro, and suggest that IFN-alpha may represent a useful tool for novel immunotherapeutic approaches in allergic disorders.
Parronchi
P
P
Division of Clinical Immunology and Allergy, University of Florence, Italy.
Mohapatra
S
S
Sampognaro
S
S
Giannarini
L
L
Wahn
U
U
Chong
P
P
Mohapatra
S
S
Maggi
E
E
Renz
H
H
Romagnani
S
S
D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant; D001483:Base Sequence; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry* / Q000145:classification / Q000187:drug effects*
D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D000939:Epitopes; D016898:Interferon-alpha; C042814:Lol p I protein, Lolium perenne; D010455:Peptides; D010940:Plant Proteins; C058089:Poa p I proteins, Poa pratensis; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007371:Interferon-gamma