Human dendritic cells acquire a semimature phenotype and lymph node homing potential through interaction with CD4+CD25+ regulatory T cells.
Interactions between dendritic cells (DC) and T cells are known to involve the delivery of signals in both directions. We sought to characterize the effects on human DC of contact with different subsets of activated CD4+ T cells. The results showed that interaction with CD25(high)CD4+ regulatory T cells (Tregs) caused DC to take on very different properties than contact with naive or memory phenotype T cells. Whereas non-Tregs stimulated DC maturation, culture with Tregs produced DC with a mixed phenotype. By many criteria, Tregs inhibited DC maturation, inducing down-regulation of costimulatory molecules and T cell stimulatory activity. However, DC exposed to Tregs also showed some changes typically associated with DC maturation, namely, increased expression of CCR7 and MHC class II molecules, and gained the ability to migrate in response to the CCR7 ligand CCL19. Both soluble factors and cell-associated molecules were shown to be involved in Treg modulation of DC, with lymphocyte activation gene 3 (LAG-3) playing a predominant role in driving maturation-associated changes. The data show that Tregs induce the generation of semimature DC with the potential to migrate into lymphoid organs, suggesting a possible mechanism by which Tregs down-modulate immune responses.
Bayry
Jagadeesh
J
The Edward Jenner Institute for Vaccine Research, University of Oxford, Compton, UK. jagadeesh.bayry@umrs681.jussieu.fr
Triebel
Frédéric
F
Kaveri
Srini V
SV
Tough
David F
DF
D015703:Antigens, CD / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D002450:Cell Communication; D002465:Cell Movement; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; C515460:CCL19 protein, human; C515370:CCR7 protein, human; D015704:CD4 Antigens; D054415:Chemokine CCL19; D019742:Chemokines, CC; D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D051193:Toll-Like Receptors; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human