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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3872-3879
IMMUNOBIOLOGY
Thymomas alter the T-cell subset composition in the blood: a
potential mechanism for thymoma-associated autoimmune disease
Viola Hoffacker,
Anja Schultz,
James J. Tiesinga,
Ralf Gold,
Berthold Schalke,
Wilfred Nix,
Reinhard Kiefer,
Hans Konrad Müller-Hermelink, and
Alexander Marx
From the Institute of Pathology, University of
Würzburg, Würzburg, Germany; New York University
Medical Center, Tisch Hospital, New York, NY; Department of
Neurology, University of Würzburg, Würzburg, Germany;
Institute of Neurology, University of Regensburg, Regensburg,
Germany; Department of Neurology, University of Mainz, Mainz,
Germany; Department of Neurology, University of Münster,
Münster, Germany.
Thymomas are the only tumors that are proven to generate mature T
cells from immature precursors. It is unknown, however, whether
intratumorous thymopoiesis has an impact on the peripheral T-cell pool
and might thus be related to the high frequency of thymoma-associated
myasthenia gravis. This study shows, using fluorescence-activated cell
sorting-based analyses and T-cell proliferation assays, that
thymopoiesis and T-cell function in thymomas correspond with
immunologic alterations in the blood. Specifically, the proportion
of circulating CD45RA+CD8+ T cells is
significantly increased in patients with thymoma compared with normal
controls, in accordance with intratumorous T-cell development that
is abnormally skewed toward the CD8+ phenotype. Moreover,
it is primarily the proportion of circulating CD45RA+CD8+ T cells that decreases after
thymectomy. The results also demonstrate that T cells reactive toward
recombinant autoantigens are distributed equally between thymomas
and blood, whereas T-cell responses to foreign antigen (ie, tetanus
toxoid) are seen only among circulating T cells and not among
thymoma-derived T cells. These functional studies support the
hypothesis that thymopoiesis occurring within thymomas alters the
peripheral T-cell repertoire. Because many thymomas are enriched with
autoantigen-specific T cells, a disturbance of circulating T-cell
subset composition by export of intratumorous T cells may contribute to
paraneoplastic autoimmune disease arising in patients with thymoma.

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