Regulatory T cells (Tregs) are essential for maintenance of self-tolerance; however, tumor cells can exploit the tolerance to escape the immune system. We investigated the Tregs frequency in patients with multiple myeloma (MM) and in those with monoclonal gammopathy of undetermined significance (MGUS), and found that CD4+FoxP3+ and CD8+FoxP3+ Tregs were significantly increased in patients with MM and correlated with the active phase. Both Tregs subsets were expanded in cocultures of CD3+ lymphocytes and fresh CD138+ MM plasma cells or RPMI8226 and U266 cell lines and functioned as natural (n) and inducible (i) Tregs insofar as they inhibited the proliferation of stimulated CD3 lymphocytes via contact-dependent and contact-independent pathways. Induction of Tregs by MM plasma cells required a contact-dependent pathway, implying antigen recognition by T cells. MM plasma cells acted as immature and tolerogenic antigen-presenting cells (APCs), in that they displayed low CD80/CD86 expression associated with a phagocytic activity. By acting as immature APCs, MM plasma cells plausibly expand (n)Tregs and (i)Tregs both through conversion of CD3+FoxP3- into CD3+FoxP3+ T cells and proliferation of CD3+FoxP3+ T cells, which may suppress the anti-MM immune response.

Myeloma cells act as tolerogenic antigen-presenting cells and induce regulatory T cells in vitro

RUGGIERI, SIMONA;DESANTIS, VANESSA;DI MARZO, LUCIA;LEONE, PATRIZIA;RACANELLI, Vito;FUMARULO, Ruggiero;VACCA, Angelo
2015-01-01

Abstract

Regulatory T cells (Tregs) are essential for maintenance of self-tolerance; however, tumor cells can exploit the tolerance to escape the immune system. We investigated the Tregs frequency in patients with multiple myeloma (MM) and in those with monoclonal gammopathy of undetermined significance (MGUS), and found that CD4+FoxP3+ and CD8+FoxP3+ Tregs were significantly increased in patients with MM and correlated with the active phase. Both Tregs subsets were expanded in cocultures of CD3+ lymphocytes and fresh CD138+ MM plasma cells or RPMI8226 and U266 cell lines and functioned as natural (n) and inducible (i) Tregs insofar as they inhibited the proliferation of stimulated CD3 lymphocytes via contact-dependent and contact-independent pathways. Induction of Tregs by MM plasma cells required a contact-dependent pathway, implying antigen recognition by T cells. MM plasma cells acted as immature and tolerogenic antigen-presenting cells (APCs), in that they displayed low CD80/CD86 expression associated with a phagocytic activity. By acting as immature APCs, MM plasma cells plausibly expand (n)Tregs and (i)Tregs both through conversion of CD3+FoxP3- into CD3+FoxP3+ T cells and proliferation of CD3+FoxP3+ T cells, which may suppress the anti-MM immune response.
File in questo prodotto:
File Dimensione Formato  
2015 European_Journal_of_Haematology.pdf

non disponibili

Descrizione: Articolo in rivista
Tipologia: Documento in Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 616.08 kB
Formato Adobe PDF
616.08 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/170911
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 18
social impact