title: Transforming growth factor-beta released by PPD-presenting malignant mesothelioma cells inhibits interferon-gamma synthesis by an anti-PPD CD4+ T-cell clone.
abstract: Besides acting complexly on both normal and tumor cells, transforming growth factor-beta (TGF-beta) can determine the nature of the response to the antigen, strongly inhibiting the differentiation of naive CD4+ T-cells toward a T helper-1 (Th-1) phenotype; in a number of experimental models, TGF-beta also appeared to be a potent immunosuppressant factor. TGF-beta was shown to be released by some human malignant mesothelioma (MMe) cells, which affects the immune response to this tumor. Thus, for a better understanding of the role of TGF-beta in the immune response to MMe cells, we evaluated the production of a Th-1 cytokine (IFN-gamma) and of a Th-2 cytokine (IL-4), following Purified Protein Derivative (PPD) recall antigen presentation by human MMe cells to a class-II major histocompatibility complex (MHC-II)-matched PPD clone (PPD clone). Our data confirm that human MMe cells possess the unusual capability of presenting a common recall antigen to CD4+ lymphocytes but also show that these tumor cells can abrogate Th-1 immune response, as evidenced by a shift in favor of the production of IL-4 over that of IFN-gamma, through a TGF-beta-mediated pathway; only the simultaneous block of TGF-beta1 and beta2 effects can significantly restore a typical Th-1 pattern of cytokine production by PPD clone in response to PPD presentation by MMe. Even though the role of TGF-beta in the promotion of MMe growth should be further and better defined, this effect should be considered when designing new therapeutical approaches aimed at improving the immune response to MMe.
authors.affiliation: Servizio di Immunologia, Università di Genova, Ospedale San Martino, Genova, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valle
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Megiovanni
authors.forename: Roberta
authors.initials: R
authors.lastname: Libener
authors.forename: Laura
authors.initials: L
authors.lastname: Mele
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudino
authors.forename: Luigi
authors.initials: L
authors.lastname: Strizzi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Guida
authors.forename: Sandro
authors.initials: S
authors.lastname: Toma
authors.forename: Luciano
authors.initials: L
authors.lastname: Mutti
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D007621:Karyotyping; D008654:Mesothelioma / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014373:Tuberculin / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D016212:Transforming Growth Factor beta; D014373:Tuberculin; D015847:Interleukin-4; D007371:Interferon-gamma