Thymopoiesis, regulatory T cells, and TCRVbeta expression in thymoma with and without myasthenia gravis, and modulatory effects of steroid therapy.
We analyzed thymocyte and thymic regulatory T cell (CD4SPCD25+Foxp3+cells, Treg) development in thymoma with and without myasthenia gravis (MG, MG-thymoma, non-MG-thymoma) and in MG-associated non-neoplastic thymus (MG-NNT). An increased number of immature CD4+CD8(-)CD3(-) thymocytes through the CD4+CD8+ to CD4+CD8(-) transition and an abnormal T cell receptor Vbeta (TCRVbeta) development through the CD4+CD8+ to CD4(-)CD8+ transition were seen both in MG-and non-MG-thymomas. Terminal thymopoiesis, i.e., CD45RA+ cells within the CD4+CD8(-)CD3+ and CD8+CD4(-)CD3+ subsets, was skewed towards the CD4+ compartment in MG-thymoma and CD8+ compartment in non-MG-thymoma, but thymic export was increased only in the latter in keeping with the hypothesis that CD8+ lymphocytes may play a role in the initial stages of autosensitization and in disagreement with the relevance of an increased output of CD4+ T lymphocytes in paraneoplastic MG. Treg level in normal thymus and MG-NNT and both MG- and non-MG-thymoma was similar, and TCRVbeta development in Treg cells was slightly altered in thymoma but irrespective of MG presence. Thus, the relevance of a defective Treg development in MG context remains to be established. Most alterations in thymopoiesis were corrected by therapeutic corticosteroid administration, and the effects of steroid administration may be mediated by thymic microenvironment.
Fattorossi
Andrea
A
Laboratory of Immunology, Oncology Department, Catholic University, Campobasso, Italy. cytogyn@rm.unicatt.it
Battaglia
Alessandra
A
Buzzonetti
Alexia
A
Minicuci
Giacomo
G
Riso
Raffaella
R
Peri
Laura
L
Scambia
Giovanni
G
Evoli
Amelia
A
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013945:Thymoma / Q000150:complications / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens; D011241:Prednisone