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.
Kronin
V
V
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Winkel
K
K
Süss
G
G
Kelso
A
A
Heath
W
W
Kirberg
J
J
von Boehmer
H
H
Shortman
K
K
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