scholarly journals B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells

2005 ◽  
Vol 102 (32) ◽  
pp. 11438-11443 ◽  
Author(s):  
S. Radhakrishnan ◽  
E. Celis ◽  
L. R. Pease
1997 ◽  
Vol 185 (10) ◽  
pp. 1743-1751 ◽  
Author(s):  
Marina Cella ◽  
Christian Döhring ◽  
Jacqueline Samaridis ◽  
Mark Dessing ◽  
Manfred Brockhaus ◽  
...  

Immunoglobulin-like transcript (ILT) 3 is a novel cell surface molecule of the immunoglobulin superfamily, which is selectively expressed by myeloid antigen presenting cells (APCs) such as monocytes, macrophages, and dendritic cells. The cytoplasmic region of ILT3 contains putative immunoreceptor tyrosine-based inhibitory motifs that suggest an inhibitory function of ILT3. Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors. Signal extinction involves SH2-containing protein tyrosine phosphatase 1, which is recruited by ILT3 upon cross-linking. ILT3 can also function in antigen capture and presentation. It is efficiently internalized upon cross-linking, and delivers its ligand to an intracellular compartment where it is processed and presented to T cells. Thus, ILT3 is a novel inhibitory receptor that can negatively regulate activation of APCs and can be used by APCs for antigen uptake.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4897-4897 ◽  
Author(s):  
Phillip Fromm ◽  
Michael Papadimitrious ◽  
Jennifer Hsu ◽  
Stephen Robert Larsen ◽  
John Gibson ◽  
...  

Abstract Dendritic cells (DC) are phenotypically identified in human blood as HLA-DR+ cells, which lack major cell surface lineage markers. We demonstrated that myeloid antigen presenting cells, including monocytes and DC display a continuum of CD14 and CD16 expression (10th Human Leucocyte Differentiation Antigen Workshop). The robustness of DC and monocyte identification, particularly when identifying cell subsets with little or no surface CD14 is limited by subjective gating strategies for determining rare cell populations. Application of Poisson counting statistics established that rare cell types such as "CD14- CD16+ DC" are often overlooked in analyses powered to detect the much larger populations of "classical" and "non-classical" monocytes. We used fluorescent and mass cytometry, in conjunction with unsupervised high dimensional clustering, to show that the continuum of CD14 expression separates CD14lo CD16+ non-classical monocytes and CD14- CD16+ DC. We have defined the CD14-CD16+ DC using a broad panel of cell surface markers and established a CD14-CD16+ DC phenotypic signature that is distinct from both classical and non-classical monocytes in healthy donor blood. The CD14-CD16+ DC differ in both size to CD14lo CD16+ monocytes and functional antigen uptake, with slower kinetics of soluble antigen uptake into lysozymes. Their proteasome processing and presentation of influenza matrix protein by MHC I was comparable to other primary blood monocytes and DC antigen presenting cell populations. The CD14-CD16+ DC had limited capacity for further in vitro differentiation. The recovery of CD14-CD16+ DC after autologous and allogeneic myeloablative hematopoietic cell transplants (HCT) followed similar kinetics to other monocytic and DC populations. CD14lo CD16+ monocytes expressed CCR5 as did other myeloid DC but CD14-CD16+ DC lacked CCR5, although interferon induced CCR5. The early differentiation and induction of CCR5 on circulating CD16+ DC after allogeneic HCT predicted for the onset of acute graft versus host disease. These data demonstrate that "CD14- CD16+ DC" represents a distinct clinically relevant human white blood cell population, whose ontogeny and function are under further investigation. Disclosures Fromm: DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Papadimitrious:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Hsu:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Larsen:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Gibson:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Bradstock:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Kupresanin:DendroCyte BioTech Ltd: Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Clark:DendroCyte BioTech Ltd: Equity Ownership, Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd. Hart:DendroCyte BioTech Ltd: Equity Ownership, Other: Laboratory IP contracted via ANZAC Research Institute to DendroCyte BioTech Ltd.


1993 ◽  
Vol 177 (2) ◽  
pp. 397-407 ◽  
Author(s):  
P G Holt ◽  
J Oliver ◽  
N Bilyk ◽  
C McMenamin ◽  
P G McMenamin ◽  
...  

Class II major histocompatibility complex (Ia)-bearing dendritic cells (DC) from airway epithelium and lung parenchyma express low-moderate antigen presenting cell (APC) activity when freshly isolated. However, this function is markedly upregulated during overnight culture in a manner analogous to epidermal Langerhans cells. The in vitro "maturation" process is inhibited by coculture with pulmonary alveolar macrophages (PAM) across a semipermeable membrane, and the degree of inhibition achieved can be markedly increased by the presence of tumor necrosis factor alpha. In addition, PAM-mediated suppression of DC function is abrogated via inhibition of the nitric oxide synthetase pathway. Functional maturation of the DC is accompanied by increased expression of surface Ia, which is also inhibited in the presence of PAM. Prior elimination of PAM from DC donors via intratracheal administration of the cytotoxic drug dichloromethylene diphosphonate in liposomes, 24-72 h before lung DC preparation, achieves a comparable upregulation of APC activity, suggesting that (consistent with the in vitro data) the resident PAM population actively suppresses the APC function of lung DC in situ. In support of the feasibility of such a regulatory mechanism, electron microscopic examination of normal lung fixed by intravascular perfusion in the inflated state (which optimally preserves PAM in situ), revealed that the majority are preferentially localized in recesses at the alveolar septal junctions. In this position, the PAM are in intimate association with the alveolar epithelial surface, and are effectively separated by as little as 0.2 microns from underlying interstitial spaces which contain the peripheral lung DC population. A similar juxtaposition of airway intraepithelial DC is demonstrated with underlying submucosal tissue macrophages, where the separation between the two cell populations is effectively the width of the basal lamina.


1986 ◽  
Vol 16 (4) ◽  
pp. 345-350 ◽  
Author(s):  
Martien L. Kapsenberg ◽  
Marcel B. M. Teunissen ◽  
Frank E. M. Stiekema ◽  
Hiskias G. Keizer

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3708-3716 ◽  
Author(s):  
D.B. Fearnley ◽  
A.D. McLellan ◽  
S.I. Mannering ◽  
B.D. Hock ◽  
D.N.J. Hart

Abstract Dendritic cells (DC) are potent antigen-presenting cells (APC) with the capacity to stimulate a primary T lymphocyte immune response and are therefore of interest for potential immunotherapeutic applications. Freshly isolated DC or DC precursors may be preferable for studies of antigen uptake and the potential control of APC costimulator activity. In this report, we report that the monoclonal antibody CMRF-44 can be used to detect early DC differentiation. The majority of DC circulating in blood do not express any known DC lineage specific markers, but can be identified by CMRF-44 labeling after a brief period of in vitro culture. The sequential acquisition of DC activation antigens allows the identification of two stages of DC maturation/activation. Cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF )α, enhance both phases of this process, whereas CD40-ligand trimer preferentially enhances the final DC maturation to a fully mature, activated phenotype. DC positively selected using CMRF-44 possess potent allostimulatory activity and are efficient at the uptake, processing, and presentation of soluble antigens for both primary and secondary immune responses. CMRF-44+ DC are also more potent than other APC types at restimulation of a chronic myeloid leukemia peptide specific T-cell clone. The use of a purified population of freshly isolated DC may be advantageous in attempts to initiate, maintain, and direct immune responses for immunotherapeutic applications.


Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3708-3716 ◽  
Author(s):  
D.B. Fearnley ◽  
A.D. McLellan ◽  
S.I. Mannering ◽  
B.D. Hock ◽  
D.N.J. Hart

Dendritic cells (DC) are potent antigen-presenting cells (APC) with the capacity to stimulate a primary T lymphocyte immune response and are therefore of interest for potential immunotherapeutic applications. Freshly isolated DC or DC precursors may be preferable for studies of antigen uptake and the potential control of APC costimulator activity. In this report, we report that the monoclonal antibody CMRF-44 can be used to detect early DC differentiation. The majority of DC circulating in blood do not express any known DC lineage specific markers, but can be identified by CMRF-44 labeling after a brief period of in vitro culture. The sequential acquisition of DC activation antigens allows the identification of two stages of DC maturation/activation. Cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF )α, enhance both phases of this process, whereas CD40-ligand trimer preferentially enhances the final DC maturation to a fully mature, activated phenotype. DC positively selected using CMRF-44 possess potent allostimulatory activity and are efficient at the uptake, processing, and presentation of soluble antigens for both primary and secondary immune responses. CMRF-44+ DC are also more potent than other APC types at restimulation of a chronic myeloid leukemia peptide specific T-cell clone. The use of a purified population of freshly isolated DC may be advantageous in attempts to initiate, maintain, and direct immune responses for immunotherapeutic applications.


1992 ◽  
Vol 284 (4) ◽  
pp. 189-192 ◽  
Author(s):  
A. Cerny ◽  
S. Izui ◽  
J. -H. Saurat ◽  
F. A. Waldvogel ◽  
H. C. Morse ◽  
...  

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