1. ¹Department of Obstetrics, Gynecology & Women's Health, University of Louisville School of Medicine, Louisville, KY 40202, USA
2. ²Department of Radiation Oncology, University of Louisville School of Medicine, Louisville, KY 40202, USA

Correspondence: Dr DD Taylor, Division of Gynecologic Oncology, University of Louisville School of Medicine, 511 South Floyd Street, MDR 420, Louisville, KY 40202, USA. E-mail: ddtaylor@louisville.edu

Received 31 August 2004; Revised 26 October 2004; Accepted 8 November 2004; Published online 18 January 2005.

Abstract

Dendritic and lymphoid 'exosomes' regulate immune activation. Tumours release membranous material mimicking these 'exosomes,' resulting in deletion of reactive lymphocytes. Tumour-derived 'exosomes' have recently been explored as vaccines, without analysis of their immunologic consequences. This investigation examines the composition of tumour-derived 'exosomes' and their effects on T lymphocytes. Membranous materials were isolated from ascites of ovarian cancer patients (n=6) and Western immunoblotting was performed for markers associated with 'exosomes.' Using cultured T cells, 'exosomes' were evaluated for suppression of CD3- and JAK 3 expressions and induction of apoptosis, measured by DNA fragmentation. 'Exosome' components mediating suppression of CD3- were isolated by continuous eluting electrophoresis and examined by Western immunoblotting. 'Exosomes' were shown to be identical with previously characterised shed membrane vesicles by protein staining and TSG101 expression. 'Exosomes' expressed class I MHC, placental alkaline phosphatase, B23/nucleophosmin, and FasL. 'Exosomes' suppressed expression of T-cell activation signalling components, CD3- and JAK 3 and induced apoptosis. CD3- suppression was mediated by two components: 26 and 42 kDa. Only the 42 kDa component reacted with anti-FasL antibody. These results indicate that, while 'exosomes' express tumour antigens, leading to their proposed utility as tumour vaccines, they also can suppress T-cell signalling molecules and induce apoptosis.