• IMMUNE NETWORK
• /
• v.12 no.3
• /
• pp.71-83
• /
• 2012

T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse.

• IMMUNE NETWORK
• /
• v.9 no.3
• /
• pp.84-89
• /
• 2009

The main stream of CD137 studies has been directed to the function of CD137 in $CD8^+$ T-cell immunity, including its anti-tumor activity, and paradoxically the immunosuppressive activity of CD137, which proves to be of a great therapeutic potential for animal models of a variety of autoimmune and inflammatory diseases. Recent studies, however, add complexes to the biology of CD137. Accumulating is evidence supporting that there exists a bidirectional signal transduction pathway for the CD137 receptor and its ligand (CD137L). CD137/CD137L interactions are involved in the network of hematopoietic and nonhematopoietic cells in addition to the well characterized antigen-presenting cell-T cell interactions. Signaling through CD137L plays a critical role in the differentiation of myeloid cells and their cellular activities, suggesting that CD137L signals trigger and sustain inflammation. The overall consequence might be that the amplified inflammation by CD137L enhances the T-cell activity together with CD137 signals by upregulating costimulatory molecules, MHC molecules, cell adhesion molecules, cytokines, and chemokines. Solving this outstanding issue is urgent and will have an important clinical implication.

• Advances in Traditional Medicine
• /
• v.4 no.1
• /
• pp.9-17
• /
• 2004

The present investigation was under taken to study whether the tumor-associated macrophages (TAM) of Daltons lymphoma (DL), a spontaneous transplantable murine T cell lymphoma can be activated to tumoricidal state by crude thymus extract. Intraperitoneal administration of thymus extract to DL-bearing mice resulted in activation of TAM with an enhanced IL-1, TNF and antigen presenting ability. It was found that treatment with thymus extract could also enhance the phagocytic and cytotoxic activity of TAM. However, only a marginal increase in arginase activity was observed. Till date to the best of our knowledge the effect of crude thymus extract on the activation of tumor associated macrophages has not been investigated, this study provides a new piece of information in the area of thymus therapy.

• IMMUNE NETWORK
• /
• v.4 no.1
• /
• pp.44-52
• /
• 2004

Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

• Molecules and Cells
• /
• v.26 no.1
• /
• pp.67-73
• /
• 2008

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. ExpreHerpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed $CD4^+$ T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of $CD4^+$ T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts $CD4^+$ T cells into the cornea.

• YAKHAK HOEJI
• /
• v.46 no.6
• /
• pp.472-476
• /
• 2002

Contact hypersensitivity (CHS) serves as a good model of cell-mediated reaction. Epidermal langerhans cell (LC) are thought to playa crucial role in the regulation of immune reaction of the skin, which elicit the CHS response by presenting Antigen to trafficking Ag-specific T cells within the skin. However, contact hypersensitivity is regarded as a negative side of immunities, caused by increased damaging immune response. Therefore, the study of effector molecule causing immune suppression is thought to be meaningful in the skin immune response. For this aim, this study investigated the influence of pedunculagin on cytokine, IL-$\beta$ expression from langerhans cell (LC). In vitro and in vivo, pedunculagin up-regulated the expression of IL-1$\beta$ mRNA. After PMA stimulation in vitro and DNFB sensitization in vivo, the expression of IL-1$\beta$ mRNA was down-regulated. This results suggested that pedunculagin could be immuno-modulator in skin immune system by modulating IL-1$\beta$ expression.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.137.2-137.2
• /
• 2003

Dendritic cells (DCs) are known to professional antigen presenting cell (APC). Due to the role as an effective activator of cytotoxic T Lymphocytes by expressing MHC, adhesion and co-stimulatory molecules, DCs are now widely recognized to play an important role in the immune responses to tumors.We investigated the effect of cultured DCs in murine melanoma pulmonary metastasis model. To follow the metastasis protocol, syngenic melanoma cells were inoculated intra-venously into the mouse (B16F10 into the C57BL/6)8 days prior to the first DC injection (1$\times$106 DCs/ mouse, i.p.) and the autologous tumor cell lysate pulsed-DCs were injected as a therapeutic module twice in two weeks. (omitted)

• Archives of Plastic Surgery
• /
• v.35 no.4
• /
• pp.367-372
• /
• 2008

Purpose: Prevention of acute rejection in skin allografts without continuous immunosuppression lacks reports in worldwide literature. Needs for chronic immunosuppression preclude the use of tissue allograft as a routine surgical reconstructive option. Recently dendritic cells(DC) gained considerable attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effects of alloantigen-pulsed dendritic cells in induction of survival increase in a rat skin allograft model. Methods: Recipient-derived dendritic cells were harvested from rat whole blood and cultured with GM-CSF(200 ng/mL) and IL-4(8 ng/mL) for 2 weeks. Then donor-specific alloantigen pulsed dendritic cells were reinjected into tail vein before skin graft. The rat dorsal skin allografts were transplanted in 5 subgroups. Groups: I) untreated, II) anti-lymphocyte serum(ALS, 0.5 mL), III) FK-506(2 mg/kg), IV) DCp, VI) DCp and FK-506. Graft appearance challenges were assessed postoperatively. Results: The group V(DC and FK-506 treated) showed longest graft survival rate(23.5 days) than other groups; untreated(5.8 days), ALS(7.2 days), FK-506 (17.5 days), DCp(12.2 days). Conclusion: Donor antigen pulsed host dendritic cell combined with short-term immunosuppression prolong skin allograft survival and has potential therapeutic application for induction of donor antigen specific tolerance.

• IMMUNE NETWORK
• /
• v.11 no.6
• /
• pp.324-335
• /
• 2011

The human leukocyte antigen (HLA), the major histocompatibility complex (MHC) in humans has been known to reside on chromosome 6 and encodes cell-surface antigen-presenting proteins and many other proteins related to immune system function. The HLA is highly polymorphic and the most genetically variable coding loci in humans. In addition to a critical role in transplantation medicine, HLA and disease associations have been widely studied across the populations worldwide and are found to be important in prediction of disease susceptibility, resistance and of evolutionary maintenance of genetic diversity. Because recently developed molecular based HLA typing has several advantages like improved specimen stability and increased resolution of HLA types, the association between HLA alleles and a given disease could be more accurately quantified. Here, in this review, we have collected HLA association data on some autoimmune diseases, infectious diseases, cancers, drug responsiveness and other diseases with unknown etiology in Koreans and attempt to summarize some remarkable HLA alleles related with specific diseases.

• IMMUNE NETWORK
• /
• v.13 no.5
• /
• pp.218-221
• /
• 2013

CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although ${\alpha}$-galactosylceramide (${\alpha}$-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-${\gamma}$ by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.