Are CD8+ dendritic cells (DC) veto cells? The role of CD8 on DC in DC development and in the regulation of CD4 and CD8 T cell responses.
The CD8-expressing dendritic cells (DC) present in mouse spleen have been shown to have a regulatory effect on the CD4 and CD8 T cells they activate, restricting subsequent T cell proliferation by either inducing apoptotic T cell death (CD4 T cells) or by limiting endogenous cytokine production (CD8 T cells). To determine the role of the CD8 molecule itself in these regulatory phenomena, the DC from CD8 null mice were studied. The DC marker DEC-205 (NLDC 145) was used as a surrogate marker for CD8, since the expression of these two molecules on splenic DC was closely correlated. DC levels were normal, and the incidence of DEC-205+ and DEC-205- DC was normal in CD8 null mice, indicating that the absence of CD8 did not affect DC development. The proliferative response of T cells to allogeneic DEC-205+ DC from either CD8-/- or CD8+/+ mice was similar and was much less than the response to DEC-205- DC from these mice. This applied to both the CD4 and the CD8 T cell responses. Thus the lack of the CD8 molecule did not affect the stimulatory or regulatory properties of the DC. The regulatory CD8+ DEC-205+ DC therefore differ in that respect from antigen-presenting 'veto' cells, where CD8 itself is involved in transmitting negative signals to the T cells. DEC-205 may prove to be a more pertinent marker of the regulatory DC population.
Kronin
V
V
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Vremec
D
D
Winkel
K
K
Classon
B J
BJ
Miller
R G
RG
Mak
T W
TW
Shortman
K
K
Süss
G
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout
D016827:CD8 Antigens