Modulation of the TCR stimulation strength can render human activated CD4+ T cells suppressive.
In this study, we explored the potential of human naive CD4(+) T cells to acquire regulatory properties upon stimulation. We demonstrated that, in vitro, pre-activated naive CD4(+)CD25(-)CD45RA(+) T cells could become anergic and suppressive CD4(+)CD25(+) T cells upon lower intensity TCR stimulation. These CD4(+)CD25(+) T cells generated in vitro potently suppress the proliferation of allogenic CD4(+)CD25(-) T cells independently of cytokines and in a contact-dependent manner. Our data indicate that expression of Foxp3 is not necessary to induce the suppressive T cell activity. We demonstrate that these CD4(+)CD25(+) T cells are unresponsive upon re-stimulation and that their suppressive activity is transient. However, we showed that the anergy and the suppressive function could be reversed by increasing the stimulus and their level of activation. We concluded from our data that these anergy and suppressive activities are related to a fine tuning of TCR activation threshold.
Noël
Grégory
G
UPRES 3889, Faculté de Médecine, Laboratoire d'Immuno-Hématologie, 2 avenue du Professeur Léon Bernard, 35043 Rennes cedex, France.
Brinster
Carine
C
Semana
Gilbert
G
Bruniquel
Denis
D
D015703:Antigens, CD / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens