Regulatory CD8+ T cells control thyrotropin receptor-specific CD4+ clones in healthy subjects.
One of the mechanisms ensuring immunological unresponsiveness or tolerance depends on the action of CD8(+) lymphocytes. In this paper, we report that, in healthy subjects, a subset of CD8(+)CD28(-) T cells suppresses the specific response to TSH receptor (TSHR) of CD4(+) clones. Suppression was highly specific, required cell-cell interaction, and was not mediated by cytotoxicity. Co-incubation of CD8(+) and CD4(+) clones, followed by the removal of the CD8(+) cells from the cultures before testing CD4(+) responsiveness to TSHR, demonstrated that CD4(+) cells were anergic since they showed low response to the antigen and a significant impairment of IL-2 production. In CD8-mediated anergy induction, the T-cell receptor (TCR) on both CD4(+) and CD8(+) cells seems to play a role. Our results indicate that one of the mechanisms ensuring peripheral tolerance involve CD8(+)CD28(-) cells. A disregulation in the control of autoreactive clones by this subset might be important for the onset of autoimmune thyroid diseases.
Molteni
Monica
M
Department of Internal Medicine, University of Milano, IRCCS Ospedale Maggiore Milano, via F. Sforza 35, 20122 Milan, Italy. monica.molteni@unisubria.it
Rossetti
Carlo
C
Scrofani
Santo
S
Bonara
Paola
P
Scorza
Raffaella
R
Kohn
Leonard D
LD
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D017635:Clonal Anergy; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011989:Receptors, Thyrotropin / Q000276:immunology*; D017634:Self Tolerance
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011989:Receptors, Thyrotropin