PMID- 11373688
OWN - NLM
STAT- MEDLINE
DCOM- 20010705
LR  - 20181130
IS  - 0027-2507 (Print)
IS  - 0027-2507 (Linking)
VI  - 68
IP  - 3
DP  - 2001 May
TI  - Dendritic cells and the control of immunity: enhancing the efficiency of antigen 
      presentation.
PG  - 160-6
AB  - BACKGROUND: Relevant antigens often are known for diseases that involve the 
      immune system. Yet purified antigens by themselves do not control immunity, 
      especially T-cell immunity. For example, many antigens have been defined for 
      HIV-1 and melanoma, but good HIV-1 vaccines and melanoma immune therapies are 
      lacking. Dendritic cells (DCs) are important intermediaries between antigens and 
      better control of the immune system. METHODS: Some properties that allow DCs to 
      control immunity are reviewed, followed by new studies using DCs as adjuvants in 
      humans. An emerging area is then detailed, the special mechanisms whereby DCs 
      enhance the formation of ligands for T-cells, i.e., complexes of major 
      histocompatibility complex (MHC) products and antigenic peptides. RESULTS: Once 
      criteria were developed to identify and isolate DCs, several functional 
      properties became evident. DCs are unusually potent in initiating T-cell mediated 
      immunity in culture. In vivo, DCs are positioned to capture antigens and migrate 
      to T-cell areas of lymphoid organs. There, DCs are able to prime animals, 
      controlling the MHC restriction of the primed T-cells and inducing resistance to 
      pathogens. DCs pulsed ex vivo with antigens are now being used to induce and 
      expand T-cell immunity in humans. To optimize their use, two areas of DC function 
      need to be harnessed: their terminal differentiation or maturation, and antigen 
      uptake. DCs capture most types of antigens at an immature stage of development, 
      but the cells must receive additional stimuli prior to acquiring potent T-cell 
      stimulatory activity. Stimuli from microbes, inflammation and trauma mature DCs. 
      These change the DCs in several ways, even inducing the formation of MHC 
      II-peptide complexes or T-cell receptor (TCR) ligands. The latter move to the 
      surface in nonlysosomal vesicles that simultaneously carry CD86 costimulatory 
      molecules for T-cell activation. Both MHC and CD86 remain co-clustered in patches 
      at the DC surface. DCs also express a receptor, DEC-205, that enhances antigen 
      uptake and presentation. DEC-205 recycles in an unusual manner through MHC class 
      II-rich, late endosomes or lysosomes, dramatically increasing the presentation of 
      bound ligands. Additionally and importantly, DCs can process dying cells and 
      immune complexes onto MHC class I products, events that are termed the "exogenous 
      pathway" or "cross presentation." CONCLUSIONS: The control of the immune system 
      by DCs reflects numerous specializations, not a single "magic bullet." These 
      specializations include a number of mechanisms that increase the efficiency of 
      antigen uptake and MHC-peptide complex formation. The harnessing of these and 
      other features of DCs provides opportunities for improving immune-based therapies 
      and vaccine design.
FAU - Steinman, R M
AU  - Steinman RM
AD  - Laboratory of Cellular Physiology and Immunology, Rockefeller University, 1230 
      York Ave, New York, NY 10021-6399, USA.
LA  - eng
GR  - AI13013/AI/NIAID NIH HHS/United States
GR  - AI40045/AI/NIAID NIH HHS/United States
PT  - Lecture
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mt Sinai J Med
JT  - The Mount Sinai journal of medicine, New York
JID - 0241032
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Immunity, Cellular
MH  - Immunotherapy/methods
MH  - Major Histocompatibility Complex/*immunology
MH  - T-Lymphocytes/immunology
EDAT- 2001/05/25 10:00
MHDA- 2001/07/06 10:01
CRDT- 2001/05/25 10:00
PHST- 2001/05/25 10:00 [pubmed]
PHST- 2001/07/06 10:01 [medline]
PHST- 2001/05/25 10:00 [entrez]
PST - ppublish
SO  - Mt Sinai J Med. 2001 May;68(3):160-6.