Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease.
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. (Blood. 2000;96:3872-3879)
Hoffacker
V
V
Institute of Pathology, University of Würzburg, Würzburg, Germany.
Schultz
A
A
Tiesinga
J J
JJ
Gold
R
R
Schalke
B
B
Nix
W
W
Kiefer
R
R
Müller-Hermelink
H K
HK
Marx
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000209:etiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D013934:Thymectomy; D013945:Thymoma / Q000097:blood* / Q000150:complications / Q000276:immunology*; D013953:Thymus Neoplasms / Q000097:blood* / Q000150:complications / Q000276:immunology*
D001324:Autoantigens; D017493:Leukocyte Common Antigens