scholarly journals Distinctive localization of antigen-presenting cells in human lymph nodes

Blood ◽  
2009 ◽  
Vol 113 (6) ◽  
pp. 1257-1267 ◽  
Author(s):  
Catherine E. Angel ◽  
Chun-Jen J. Chen ◽  
Oliver C. Horlacher ◽  
Sintia Winkler ◽  
Thomas John ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Lymphocytes ◽  
Lymph Nodes ◽  
T Lymphocyte ◽  
Close Contact ◽  
Antigen Presenting Cells ◽  
Lymphocyte Responses ◽  
Antigen Presenting ◽  
Medullary Cords

Abstract Professional antigen-presenting cells (APCs) are sentinel cells of the immune system that present antigen to T lymphocytes and mediate an appropriate immune response. It is therefore surprising that knowledge of the professional APCs in human lymph nodes is limited. Using 3-color immunohistochemistry, we have identified APCs in human lymph nodes, excluding plasmacytoid APCs, that fall into 2 nonoverlapping classes: (1) CD209+ APCs, coexpressing combinations of CD206, CD14, and CD68, that occupied the medullary cords, lined the capsule and trabeculae and were also scattered throughout the diffuse T-lymphocyte areas of the paracortex; and (2) APCs expressing combinations of CD1a, CD207, and CD208, that were always restricted to the paracortex. Surprisingly, this second class of APCs was almost entirely absent from many lymph nodes. Our data suggest that most CD208+ cells, often referred to as “interdigitating cells,” derive from migratory APCs, and that the major APC subset consistently resident in the paracortex of human lymph nodes is the CD209+ subset. All APC subsets were demonstrated to be in close contact with the fibroreticular network. The identification of 2 distinct APC populations in the paracortex of human lymph nodes has important implications for understanding T-lymphocyte responses and optimizing vaccine design.

scholarly journals Selective Induction of Apoptosis in Antigen-Presenting Cells in Mice by Parapoxvirus ovis

2001 ◽  
Vol 75 (10) ◽  
pp. 4699-4704 ◽  
Author(s):  
Nicole Kruse ◽  
Olaf Weber
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Antigen Presenting Cells ◽  
T Cell Response ◽  
Survival Strategy ◽  
Short Intervals ◽  
Induction Of Apoptosis ◽  
Parapoxvirus Ovis ◽  
Antigen Presenting ◽  
Mouse System

ABSTRACT Viruses have evolved numerous mechanisms to avoid host immune reactions. Here we report a mechanism by which Parapoxvirus ovis (PPVO) interferes with antigen presentation. PPVO (orf virus) causes orf, an acute skin disease of sheep and goats worldwide. Importantly, PPVO can repeatedly infect its host in spite of a vigorous inflammatory and host immune response to the infection. We demonstrate in a mouse system that PPVO induces apoptosis in a significant number of antigen-presenting cells after intraperitoneal injection using the CD95 pathway, thus preventing a primary T-cell response. We also show that PPVO induces a compensatory activation of the immune system. Our results may help to explain the phenomenon that natural PPVO infections in sheep occur repeatedly even after short intervals. They also suggest that the combination of immunosuppressive and immunostimulatory mechanisms is an effective survival strategy that might be used in other viruses as well.

GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2037-2044 ◽  
Author(s):  
Nicolas Cohen ◽  
Enguerran Mouly ◽  
Haifa Hamdi ◽  
Marie-Christine Maillot ◽  
Marc Pallardy ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Leucine Zipper ◽  
Transforming Growth Factor ◽  
Cd40 Ligand ◽  
Dc Functions ◽  
Circulating Antigen ◽  
Lymphocyte Responses ◽  
Antigen Presenting

Interleukin (IL)-10 and glucocorticoids (GCs) inhibit the ability of antigen-presenting dendritic cells (DCs) to stimulate T lymphocytes. We show that induction of GILZ (GC-induced leucine zipper) is involved in this phenomenon. IL-10, dexamethasone (DEX), and transforming growth factor (TGF)β stimulate GILZ production in human immature DCs derived from monocytes and from CD34+ cells. GILZ is necessary and sufficient for DEX, IL-10, and TGFβ modulation of CD80, CD83, CD86, immunoglobulin-like transcript (ILT)-3, and B7-H1 expression by DCs, and alteration of DC functions. GILZ stimulates the production of IL-10 by immature DCs and prevents the production of inflammatory chemokines by CD40L-activated DCs. In contrast, GILZ does not prevent CD40 ligand-mediated inhibition of phagocytosis, indicating that it affects some but not all aspects of DC maturation. GILZ prevents DCs from activating antigen-specific T lymphocyte responses. Administration of GCs to patients stimulates GILZ expression in their circulating antigen-presenting cells, and this contributes to the weak lymphocyte responses of GC-treated patients. Thus, regulation of GILZ expression is an important factor determining the decision of DCs whether or not to stimulate T lymphocytes, and IL-10, GCs, and TGFβ share this mechanism for influencing DC functions and the balance between immune response and tolerance.

T-lymphocyte responses to the human telomerase reverse transcriptase (hTERT) in patients (pts) with advanced non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3061-3061
Author(s):  
E. Fabre ◽  
J. Medioni ◽  
M. Dosset ◽  
M. Dosset ◽  
E. Tartour ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Smoking Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Therapeutic Vaccine ◽  
Stage Iii ◽  
Human Telomerase Reverse Transcriptase ◽  
Lymphocyte Responses

3061 Background: hTERT is a potential target for cancer immunotherapy because it is highly expressed in tumor cells. To assess the applicability of hTERT-based immunotherapy in NSCLC, we aimed to analyse the natural anti-hTERT T-lymphocyte responses in advanced NSCLC pts. Methods: We included in a prospective, monocentric study chemonaive NSCLC pts. Pts were required to present stage III or IV tumor, without any immune deficiency or immunosuppressive drug. Before start of chemotherapy, the anti-hTERT T-lymphocyte responses were assessed in whole blood by ELISPOT and thymidine proliferation test. We evaluated the presence or absence of hTERT-specific T lymphocytes. Thereafter, we analyzed its link with age (< 60 vs. ≥ 60 yrs), ECOG performance status PS (0–1 vs. 2–3), tumoral stage (III vs. IV), histological subtype (adenocarcinoma vs. other), and smoking status (never smoker vs. smoker). Statistical analysis was performed using chi-square or Fischer test. Results: Between February and September 2008, 31 NSCLC pts were included. They presented a stage III (n = 6) or IV (n = 27) disease. Median age was 65 yrs (33–89). Eighteen pts presented anti-hTERT T lymphocytes (54%); among them we found 12 pts ≥ 60 yrs (70%), 14 adenocarcinoma (77%), 13 stage IV (72%), 7 pts with PS 2/3 (41%), and 13 smokers (72%). So far, univariate analysis showed no relationship between presence of anti-hTERT T-cell responses and pts’ characteristics. Conclusions: These preliminary results demonstrate that natural anti-hTERT immune response exists in NSCLC pts, even in case of poor prognosis. Thus, clinical trial using telomerase-based therapeutic vaccine may include NSCLC pts with advanced disease. The study is ongoing to evaluate if baseline anti-hTERT immune response could be used as selection criteria for telomerase vaccination in NSCLC. No significant financial relationships to disclose.

Recruitment of different subsets of antigen-presenting cells selectively modulates DNA vaccine-elicited CD4+ and CD8+ T lymphocyte responses

2004 ◽  
Vol 34 (4) ◽  
pp. 1011-1020 ◽  
Author(s):  
Paul F. McKay ◽  
Dan H. Barouch ◽  
Sampa Santra ◽  
Shawn M. Sumida ◽  
Shawn S. Jackson ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Cd8 T Lymphocyte ◽  
Lymphocyte Responses ◽  
Antigen Presenting

scholarly journals Bone Marrow–Derived Antigen-Presenting Cells Are Required for the Generation of Cytotoxic T Lymphocyte Responses to Viruses and Use Transporter Associated with Antigen Presentation (Tap)-Dependent and -Independent Pathways of Antigen Presentation

2000 ◽  
Vol 192 (8) ◽  
pp. 1143-1150 ◽  
Author(s):  
Luis J. Sigal ◽  
Kenneth L. Rock
Keyword(s):  
Bone Marrow ◽  
Antigen Presentation ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Lymphocytic Choriomeningitis ◽  
Ctl Response ◽  
Lymphocyte Responses ◽  
Antigen Presenting ◽  
Ctl Responses

Bone marrow (BM)-derived professional antigen-presenting cells (pAPCs) are required for the generation of cytotoxic T lymphocyte (CTL) responses to vaccinia virus and poliovirus. Furthermore, these BM-derived pAPCs require a functional transporter associated with antigen presentation (TAP). In this report we analyze the requirements for BM-derived pAPCs and TAP in the initiation of CTL responses to lymphocytic choriomeningitis virus (LCMV) and influenza virus (Flu). Our results indicate a requirement for BM-derived pAPCs for the CTL responses to these viruses. However, we found that the generation of CTLs to one LCMV epitope (LCMV nucleoprotein 396–404) was dependent on BM-derived pAPCs but, surprisingly, TAP independent. The study of the CTL response to Flu confirmed the existence of this BM-derived pAPC-dependent/TAP-independent CTL response and indicated that the TAP-independent pathway is ∼10–300-fold less efficient than the TAP-dependent pathway.

scholarly journals HLA-DR1–Restricted bcr-abl (b3a2)-Specific CD4+ T Lymphocytes Respond to Dendritic Cells Pulsed With b3a2 Peptide and Antigen-Presenting Cells Exposed to b3a2 Containing Cell Lysates

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 290-297 ◽  
Author(s):  
S.I. Mannering ◽  
J.L. McKenzie ◽  
D.B. Fearnley ◽  
D.N.J. Hart
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Fusion Gene ◽  
Antigen Presenting Cells ◽  
Break Point ◽  
Chromosome 9 ◽  
Protein Fusion ◽  
Peptide Epitope ◽  
Cell Lysates ◽  
Antigen Presenting

Chronic myeloid leukemia (CML) is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster region (bcr) on chromosome 22, t(9; 22) (q34; q11). This translocation results in the expression of a 210-kD bcr-abl protein fusion gene product. The juxtaposition of the bcr and abl genes produces a novel junctional amino acid sequence, which may be presented by antigen-presenting cells and recognized specifically by human T lymphocytes. We have generated a CD4+ T lymphocyte line (NG-1) which recognizes the peptide epitope (GFKQSSKALQR) in association with HLA-DRβ1*0101-02. A comparison of antigen-presenting cells showed that CMRF-44+ blood dendritic cell presented a 12mer b3a2 peptide effectively. The b3a2 peptide was able to generate specific primary T-lymphocyte responses in other HLA-DR1 donors. We also show that bcr-abl, b3a2 peptide-specific T-lymphocyte lines proliferate in response to bcr-abl b3a2 containing cell lysates (K562 or CML PBMC derived) but not control (including b2a2 CML PBMC) lysates.

scholarly journals HLA-DR1–Restricted bcr-abl (b3a2)-Specific CD4+ T Lymphocytes Respond to Dendritic Cells Pulsed With b3a2 Peptide and Antigen-Presenting Cells Exposed to b3a2 Containing Cell Lysates

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 290-297 ◽  
Author(s):  
S.I. Mannering ◽  
J.L. McKenzie ◽  
D.B. Fearnley ◽  
D.N.J. Hart
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Fusion Gene ◽  
Antigen Presenting Cells ◽  
Break Point ◽  
Chromosome 9 ◽  
Protein Fusion ◽  
Peptide Epitope ◽  
Cell Lysates ◽  
Antigen Presenting

Abstract Chronic myeloid leukemia (CML) is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster region (bcr) on chromosome 22, t(9; 22) (q34; q11). This translocation results in the expression of a 210-kD bcr-abl protein fusion gene product. The juxtaposition of the bcr and abl genes produces a novel junctional amino acid sequence, which may be presented by antigen-presenting cells and recognized specifically by human T lymphocytes. We have generated a CD4+ T lymphocyte line (NG-1) which recognizes the peptide epitope (GFKQSSKALQR) in association with HLA-DRβ1*0101-02. A comparison of antigen-presenting cells showed that CMRF-44+ blood dendritic cell presented a 12mer b3a2 peptide effectively. The b3a2 peptide was able to generate specific primary T-lymphocyte responses in other HLA-DR1 donors. We also show that bcr-abl, b3a2 peptide-specific T-lymphocyte lines proliferate in response to bcr-abl b3a2 containing cell lysates (K562 or CML PBMC derived) but not control (including b2a2 CML PBMC) lysates.

Hsp90 Is Critical for the Regulation of Phenotype and Functionality of Human Dendritic Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2401-2401
Author(s):  
Jooeun Bae ◽  
Constantine Mitsiades ◽  
Tai Yu-Tzu ◽  
Jeff Martinson ◽  
Ramesh Babu Batchu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
T Lymphocytes ◽  
Clinical Data ◽  
Antigen Presenting Cells ◽  
Hsp90 Inhibitor ◽  
Antigen Uptake ◽  
Dc Function ◽  
Antigen Presenting ◽  
Inhibitor Treatment

Abstract Hsp90, a molecular chaperone, plays a critical role in protein folding and transport, and thereby it modulates cellular activity. Pre-clinical data shows over-expression of Hsp90 in multiple myeloma (MM) and efficacy of Hsp90 inhibitor in myeloma has been determined in vitro. Based on these results, phase I/II trial evaluating clinical efficacy of the Hsp90 inhibitor is underway in MM. Although Hsp90 inhibitor shows significant effects on tumor cells, there is limited information concerning its effects on the immune system. The objective of this study was to evaluate the effects of Geldanamycin on activity of antigen-presenting cells. Immature and mature monocyte derived dendritic cells (DC) from normal human donors were used as the source of antigen-presenting cells in this study. Geldanamycin treatment of DC for 24 hours had no effect on cell viability (>90%), however, it led to a significant down-regulation of surface antigens associated with activation (CD86, CD80), maturation (CD83) and antigen presentation (HLA-ABC, HLA-DPQR). This decline was associated with changes in gene expression levels of these antigens, however the protein expression analyzed by % positive cells was not down-regulated with the treatment. Exposure to Hsp90 inhibitor was associated with significant decreases in IL-12 secretion (untrt vs. trt = 135 vs. 21 pg/ml), antigen uptake (MFI untrt 798 vs. MFI trt 449, Dextran-FITC), and antigen processing. These changes were associated with decline in DC function, which were demonstrated by significant decrease in Hsp90-treated DC compared to untreated DC in presentation of Tetanus Toxoid to autologous T lymphocytes (untrt vs. trt = 73 % vs. 47 %, CFSE proliferation), allogeneic T lymphocytes stimulation (untrt vs. trt = 232795 cpm vs. 116876 cpm, 3H-thymidine incorporation), and induction of IFN-g secretion from allogenic T lymphocytes (untrt vs. trt = 500 vs. 30 pg/ml). Taken together, these results show significant decline in DC function following Hsp90 inhibitor treatment. Further studies are underway using MM patient samples pre- and post-Hsp90 inhibitor treatment to understand in vivo effects on the immune system. Our pre-clinical data suggests the need to consider proper sequence of various therapeutic modalities, including immunotherapy, to optimize and improve clinical outcome.

The role of bacterial super antigens in the immune response: From biology to cancer treatment

2020 ◽  
Vol 16 ◽  
Author(s):  
Behnam Emamgolizadeh Gurt Tapeh ◽  
Mohammad Sadegh Hashemzadeh ◽  
Ali Mir Hoseini
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Lymphocytes ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Vector Systems ◽  
Bacterial Vector ◽  
Antigen Presenting ◽  
Stimulation Of

Aims: Encouraging results have been indicated preclinically and in patients using the bacterial super antigen. This review article intends to summarize the role of the super antigens that have been recently used in the treatment of cancer. In addition, the vector systems including lentiviral vectors, adeno-associated vector systems and retroviral vectors that are increasingly being used in basic and applied research were discussed. Most importantly, the new CRISPR technique has also been discussed in this literature review. Discussion: More successful therapies can be achieved by manipulating bacterial vector systems through incorporating genes related to the super antigens and cytokines. The products of SAg and cytokine genes contributes to the strong stimulation of immune system against tumor cells. They bind to MHC II molecules as well as the V beta regions of TCR and lead to the production of IL2 and other cytokines, the activation of antigen-presenting cells and T lymphocytes. Additionally, super antigens can be used to eradicate tumor cells. Better results in cancer treatment can be achieved by transferring super antigen genes and subsequent strong immune stimulation along with other cancer immunotherapy agents. Conclusion: Super antigens induce the proliferation of T lymphocytes and antigen-presenting cells by binding to MHCII molecules and V beta regions in T cell receptors. Therefore, the presentation of tumor cell antigens is increased. Additionally, the production of important cytokines by T cells and APCs contributes to the stimulation of immune response against tumor cells. The manipulation of bacterial vector systems through incorporating genes related to SAgs and other immune response factors is a good strategy for immune system stimulating and eradicating of tumor cells along with other immunotherapy agents.

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