Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes.
CD8+CD25+ cells, which expressed high levels of Foxp3, glucocorticoid-induced tumor necrosis factor receptor (GITR), CCR8, tumor necrosis factor receptor 2 (TNFR2), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) mRNAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8+CD25+ thymocytes did not produce cytokines, but most of them expressed surface CTLA-4 and transforming growth factor beta1 (TGF-beta1). Like CD4+CD25+, CD8+CD25+ thymocytes suppressed the proliferation of autologous CD25-T cells via a contact-dependent mechanism. The suppressive activity of CD8+CD25+ thymocytes was abrogated by a mixture of anti-CTLA-4 and anti-TGF-beta1 antibodies and it was mediated by their ability to inhibit the expression of the interleukin 2 receptor alpha chain on target T cells. These results demonstrate the existence of a subset of human CD8+CD25+ thymocytes sharing phenotype, functional features, and mechanism of action with CD4+CD25+ T regulatory cells.
Cosmi
Lorenzo
L
Dipartimento di Medicina Interna, Viale Morgagni 85, Firenze 50134, Italy.
Liotta
Francesco
F
Lazzeri
Elena
E
Francalanci
Michela
M
Angeli
Roberta
R
Mazzinghi
Benedetta
B
Santarlasci
Veronica
V
Manetti
Roberto
R
Vanini
Vittorio
V
Romagnani
Paola
P
Maggi
Enrico
E
Romagnani
Sergio
S
Annunziato
Francesco
F
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D016176:T-Lymphocyte Subsets; D013950:Thymus Gland / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology; D053773:Transforming Growth Factor beta1
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D007376:Interleukin-2; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1