PMID- 15004177
OWN - NLM
STAT- MEDLINE
DCOM- 20040713
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 172
IP  - 6
DP  - 2004 Mar 15
TI  - Increased dendritic cell numbers impair protective immunity to intracellular 
      bacteria despite augmenting antigen-specific CD8+ T lymphocyte responses.
PG  - 3725-35
AB  - Dendritic cells (DCs) reside in tissues, where they function as sentinels, 
      providing an essential link between innate and adaptive immunity. Increasing the 
      numbers of DCs in vivo augments T cell responses, and can cause dramatic 
      CTL-dependent tumor regression. To determine whether greater DC numbers promoted 
      T cell-mediated protection in the context of host defense against intracellular 
      bacteria, we treated mice with Flt3 ligand (Flt3-L) to increase DCs in vivo and 
      challenged them with Listeria monocytogenes. Unexpectedly, after primary 
      challenge with Listeria, the overall control of Listeria infection was impaired 
      in Flt3-L-treated mice, which had greater bacterial burden and mortality than 
      controls. Similar results were obtained when DC numbers were increased by 
      treatment with polyethylene glycol-conjugated GM-CSF rather than Flt3-L and in 
      mice infected with Mycobacterium tuberculosis. Impaired protection was not due to 
      dysfunctional T cell responses, as Flt3-L-treated mice had a greater frequency 
      and absolute number of Ag-specific CD8+ T cells, which produced IFN-gamma, 
      exhibited cytolytic activity, and transferred protection. The increased Listeria 
      burden in Flt3-L-treated mice was preferentially associated with DCs, which were 
      unable to kill Listeria and more resistant to CTL lysis compared with macrophages 
      in vitro. Although we cannot exclude the possibility that other potential 
      effects, in addition to increased numbers of DCs, are shared by Flt3-L and 
      polyethylene glycol-conjugated GM-CSF and contributed to the increase in 
      susceptibility observed in treated mice, these results support the notion that DC 
      numbers must be properly controlled within physiological limits to optimize host 
      defense to intracellular bacterial pathogens.
FAU - Alaniz, Robert C
AU  - Alaniz RC
AD  - Department of Immunology, University of Washington, Seattle, WA 98195, USA.
FAU - Sandall, Sharsti
AU  - Sandall S
FAU - Thomas, Elaine K
AU  - Thomas EK
FAU - Wilson, Christopher B
AU  - Wilson CB
LA  - eng
GR  - HD18184/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - 0 (flt3 ligand protein)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cell Count
MH  - Cell Division/immunology
MH  - Cells, Cultured
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology/*microbiology/pathology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage
MH  - Humans
MH  - Immunity, Cellular
MH  - Immunity, Innate
MH  - Immunosuppressive Agents/administration & dosage
MH  - Injections, Intraperitoneal
MH  - Intracellular Fluid/*immunology/*microbiology
MH  - Ligands
MH  - Listeria monocytogenes/growth & development/immunology
MH  - Listeriosis/immunology/microbiology/pathology
MH  - Membrane Proteins/administration & dosage
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Polyethylene Glycols/administration & dosage
MH  - Tuberculosis/immunology/microbiology/pathology
EDAT- 2004/03/09 05:00
MHDA- 2004/07/14 05:00
CRDT- 2004/03/09 05:00
PHST- 2004/03/09 05:00 [pubmed]
PHST- 2004/07/14 05:00 [medline]
PHST- 2004/03/09 05:00 [entrez]
AID - 10.4049/jimmunol.172.6.3725 [doi]
PST - ppublish
SO  - J Immunol. 2004 Mar 15;172(6):3725-35. doi: 10.4049/jimmunol.172.6.3725.