A subclass of dendritic cells regulates the response of naive CD8 T cells by limiting their IL-2 production.
Previous work indicated that a subclass of mouse spleen dendritic cells (DC), those bearing CD8alpha, expresses the Fas ligand and restricts peripheral CD4 T cell responses by initiating Fas-mediated apoptosis. To determine whether a similar regulation applies to CD8 T cells, they were purified from normal or from TCR-transgenic mice, and then cultured with purified splenic CD8+ DC or CD8- DC presenting either alloantigens or the specific Ag for the TCR transgene. In all systems studied, the proliferative response of CD8 T cells was markedly less on stimulation with CD8+ DC compared with conventional CD8- DC. However, the basis of this restricted proliferation in response to CD8+ DC was totally different for CD8 T cells than for CD4 T cells. The reduced proliferation of CD8 T cells occurred later in the response than with CD4 T cells. In contrast with CD4 T cells, the reduced proliferation of CD8 T cells occurred even with T cells from Fas-deficient Ipr mice, or with DC from Fas ligand-deficient gld mice, indicating that Fas-induced apoptosis was not involved. Also, in contrast with CD4 T cells, the reduced proliferation of CD8 T cells was completely reversed by the addition of exogenous IL-2. Furthermore, cultures of CD8 T cells with CD8+ DC were found to be deficient in IL-2 production. Accordingly, although CD8+ DC are very efficient at stimulating CD8 T cells into cell division, they are deficient at stimulating endogenous cytokine production. The implications of these different DC regulatory systems are discussed.
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
V
V
Kronin
K
K
Winkel
G
G
Süss
A
A
Kelso
W
W
Heath
J
J
Kirberg
H
H
von Boehmer
K
K
Shortman
D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D019014:fas Receptor