CD4+CD25+ T cells as immunoregulatory T cells in vitro.
We have further characterized the in vitro phenotype and function of anergic and suppressive CD4(+)25(+) T cells. Following TCR ligation, DO.11.10 CD4(+)25(+) T cells suppress the activation of OT-1 CD8(+)25(-) T cells in an antigen nonspecific manner. Although suppression was seen when using a mixture of APC from both parental strains, it was very much more marked when using F1 APC. APC pretreated with, and then separated from CD4(+)25(+) T cells did not have diminished T cell costimulatory function, suggesting that APC are not the direct targets of CD4(+)25(+) T cell regulation. CTLA-4 blockade failed to abrogate suppression by CD4(+)25(+) T cells in mixing experiments. Although CD4(+)25(+) T cells failed to respond following cross-linking of TCR, they could be induced to proliferate following the addition of exogenous IL-2, allowing the generation of a T cell line from CD4(+)25(+) T cells. After the first in vitro restimulation, CD4(+)25(+) T cells were still anergic and suppressive following TCR engagement. However, after three rounds of restimulation, their anergic and suppressive status was abrogated.
Chai
Jian-Guo
JG
MRC Transplantation Biology Group, Clinical Sciences Centre, Imperial College School of Medicine, London, GB, UK. jianguo.chai@csc.mrc.ac.uk
Tsang
Julia Y S
JY
Lechler
Robert
R
Simpson
Elizabeth
E
Dyson
Julian
J
Scott
Diane
D
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology; D053222:Fas Ligand Protein; D018796:Immunoconjugates; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019014:fas Receptor; D000069594:Abatacept