Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA‐4 expression

• Published in: European journal of immunology Vol. 34; no. 12; pp. 3485 - 3496
• Main Authors: Birebent, Brigitte, Lorho, Richard, Lechartier, Hélène, de Guibert, Sophie, Alizadeh, Mehdi, Vu, Nicolas, Beauplet, Alain, Robillard, Nelly, Semana, Gilbert
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.12.2004
• Subjects: Antigens, CD; Antigens, Differentiation - genetics; Antigens, Differentiation - immunology; Antigens, Differentiation - metabolism; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CTLA-4 Antigen; CTLA‐4; Cytokines - metabolism; Human; Humans; Ionomycin - pharmacology; Ionophores - pharmacology; Receptors, Interleukin-2 - immunology; Regulatory T cell
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200324632

It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4+CD25+ T cell compartment. Here, we describe an original method to purify human CD4+CD25+CD152+ T lymphocytes as living cells by forcing the exportation of CTLA‐4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4+CD25+ T cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T cells is associated with an increased expression of Foxp3 and that CD4+CD25+CD152+ T lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen‐specific T cells than CD4+CD25+CD152– T lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA‐4, we demonstrate that indeed CTLA‐4 is involved in CD4+CD25+CD152+ T cell regulatory activity, while suppressive cytokines are not.