Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA-4 expression.
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.
Birebent
Brigitte
B
Laboratoire d'Immunologie (UPRES EA 1257-IFR97), Faculté de Médecine de Rennes1, Rennes, France.
Lorho
Richard
R
Lechartier
Hélène
H
de Guibert
Sophie
S
Alizadeh
Mehdi
M
Vu
Nicolas
N
Beauplet
Alain
A
Robillard
Nelly
N
Semana
Gilbert
G
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D007476:Ionophores; D015375:Receptors, Interleukin-2; D015759:Ionomycin