DC-induced CD8(+) T-cell response is inhibited by MHC class II-dependent DX5(+)CD4(+) Treg.
CD4(+) T cells are important for CD8(+) T-cell priming by providing cognate signals for DC maturation. We analyzed the capacity of CD4(+) T cells to influence CD8(+) T-cell responses induced by activated DC. Surprisingly, mice depleted for CD4(+) cells were able to generate stronger antigen-specific CD8(+) T-cell responses after DC vaccination than non-depleted mice. The same observation was made when mice were vaccinated with MHC class II(-/-) DC, indicating the presence of a MHC class II-dependent CD4(+) T-cell population inhibiting CD8(+) T-cell responses. Recently we described the expansion of DX5(+)CD4(+) T cells, a T-cell population displaying immune regulatory properties, upon vaccination with DC. Intriguingly, we now observe an inverse correlation between CD8(+) T-cell induction and expansion of DX5(+)CD4(+) T cells as the latter cells did not expand after vaccination with MHC class II(-/-) DC. In vitro, DX5(+)CD4(+) T cells were able to limit proliferation, modulate cytokine production and induce Foxp3(+) expression in OVA-specific CD8(+) T cells. Together, our data show an inhibitory role of CD4(+) T cells on the induction of CD8(+) T-cell responses by activated DC and indicate the involvement of DX5(+)CD4(+), but not CD4(+)CD25(+), T cells in this process.
Han
Wanda G H
WG
Department of Rheumatology, Leiden University Medical Center, The Netherlands. W.G.H.Han@LUMC.nl
Schuurhuis
Danita H
DH
Fu
Nathalie
N
Camps
Marcel
M
van Duivenvoorde
Leonie M
LM
Louis-Plence
Pascale
P
Franken
Kees L M C
KL
Huizinga
Tom W J
TW
Melief
Cornelis J M
CJ
Toes
René E M
RE
Ossendorp
Ferry
F
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D039421:Integrin alpha2 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014611:Vaccination / Q000379:methods
D000906:Antibodies; D000949:Histocompatibility Antigens Class II; C508018:Il2ra protein, mouse; D039421:Integrin alpha2; D053645:Interleukin-2 Receptor alpha Subunit