Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood.
A subpopulation of peripheral human CD4(+)CD25(+) T cells that expresses CD45RO, histocompatibility leukocyte antigen DR, and intracellular cytotoxic T lymphocyte-associated antigen (CTLA) 4 does not expand after stimulation and markedly suppresses the expansion of conventional T cells in a contact-dependent manner. After activation, CD4(+)CD25(+) T cells express CTLA-4 on the surface detectable for several weeks. These cells show a G1/G0 cell cycle arrest and no production of interleukin (IL)-2, IL-4, or interferon (IFN)-gamma on either protein or mRNA levels. The anergic state of CD4(+)CD25(+) T cells is not reversible by the addition of anti-CD28, anti-CTLA-4, anti-transforming growth factor beta, or anti-IL-10 antibody. However, the refractory state of CD4(+)CD25(+) T cells was partially reversible by the addition of IL-2 or IL-4. These data demonstrate that human blood contains a resident T cell population with potent regulatory properties.
Jonuleit
H
H
Department of Dermatology, University of Mainz, D-55101 Mainz, Germany. jonuleit@hautklinik.klinik.uni-mainz.de
Schmitt
E
E
Stassen
M
M
Tuettenberg
A
A
Knop
J
J
Enk
A H
AH
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis*; D060908:CTLA-4 Antigen; D002450:Cell Communication; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D015375:Receptors, Interleukin-2; D000069594:Abatacept; D017493:Leukocyte Common Antigens