Transforming growth factor-beta released by PPD-presenting malignant mesothelioma cells inhibits interferon-gamma synthesis by an anti-PPD CD4+ T-cell clone.

Maria Teresa Valle, Camillo Porta, Anna Maria Megiovanni, Roberta Libener, Laura Mele, Giovanni Gaudino, Luigi Strizzi, Raffaele Guida, Sandro Toma, Luciano Mutti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalInternational Journal of Molecular Medicine
Volume11
Issue number2
Publication statusPublished - Feb 2003

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Transforming growth factor-beta released by PPD-presenting malignant mesothelioma cells inhibits interferon-gamma synthesis by an anti-PPD CD4+ T-cell clone.'. Together they form a unique fingerprint.

Cite this