Life of T Follicular Helper Cells

서웅경 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.3

Antibodies are powerful defense tools against pathogens but may cause autoimmune diseases when erroneously directed toward self-antigens. Thus, antibody producing cells are carefully selected, refined, and expanded in a highly regulated microenvironment (germinal center) in the peripheral lymphoid organs. A subset of T cells termed T follicular helper cells (Tfh) play a central role in instructing B cells to form a repertoire of antibody producing cells that provide life-long supply of high affinity, pathogenspecific antibodies. Therefore, understanding how Tfh cells arise and how they facilitate B cell selection and differentiation during germinal center reaction is critical to improve vaccines and better treat autoimmune diseases. In this review, I will summarise recent findings on molecular and cellular mechanisms underlying Tfh generation and function with an emphasis on T cell costimulation.

Life of T Follicular Helper Cells

Suh, Woong-Kyung Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.3

Antibodies are powerful defense tools against pathogens but may cause autoimmune diseases when erroneously directed toward self-antigens. Thus, antibody producing cells are carefully selected, refined, and expanded in a highly regulated microenvironment (germinal center) in the peripheral lymphoid organs. A subset of T cells termed T follicular helper cells (Tfh) play a central role in instructing B cells to form a repertoire of antibody producing cells that provide life-long supply of high affinity, pathogenspecific antibodies. Therefore, understanding how Tfh cells arise and how they facilitate B cell selection and differentiation during germinal center reaction is critical to improve vaccines and better treat autoimmune diseases. In this review, I will summarise recent findings on molecular and cellular mechanisms underlying Tfh generation and function with an emphasis on T cell costimulation.

CTLA4-Ig 융합단백의 T세포 증식 및 B세포 항체생산 억제 효과

장성옥 ( Jang Seong Og ),이소연 ( Lee So Yeon ),홍수종 ( Hong Su Jong ) 대한천식알레르기학회 2003 천식 및 알레르기 Vol.23 No.4

Split peripheral tolerance: CD40 ligation blocks tolerance induction for CD8 T cells but not for CD4 T cells in response to intestinal antigens

Chung, Yeonseok,Ko, Sung-Youl,Ko, Hyun-Jeong,Kang, Chang-Yuil WILEY-VCH Verlag 2005 European journal of immunology Vol.35 No.5

<P>The role of antigen-presenting cells in the balance between immunity and tolerance to intestinal antigens remains poorly understood. In this study, we examined whether CD40 ligation affects the induction of CD4 and CD8 T cell tolerance in response to intestinal antigens. We show that an agonistic anti-CD40 mAb treatment did not block the induction of OVA-specific CD4 T cell tolerance, whereas this approach enabled strong priming of OVA-specific cytotoxic T cells (CTL), preventing CTL tolerance to intestinal antigen. Such CTL priming was independent of CD4 T cell help but required B7 costimulation. Co-administration of anti-CD40 mAb increased the synthesis of IL-2 and the expression of CD25 by CD8 T cells, but neither IL-2 production nor CD25 expression by CD4 T cells was enhanced by anti-CD40 mAb. However, neutralization of TGF-&bgr; together with addition of agonistic anti-CD40 mAb was able to reverse CD4 T cell tolerance. These findings suggest that the induction of tolerance versus immunity against intestinal antigens is determined by the status of the antigen-presenting cells and that signals via CD40 differently regulate the outcome of CD4 and CD8 T cells in vivo.</P>

Osteoimmunology : Interplay Between the Immune System and Bone Metabolism

C.Walsh, Matthew,Kim, Nacksung,Kadono, Yuho,Rho, Jaerang,Lee, Soo Young,Lorenzo, Joseph,Choi, Yongwon 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

Studies of bone and the immune system have converged in recent years under the banner of osteoimmunology. The immune system is spawned in the bone marrow reservoir, and investigators now recognize that important niches also exist there for memory lymphocytes. At the same time, various factors produced during immune responses are capable of profoundly affecting regulation of bone. Mechanisms have evolved to prevent excessive interference by thc immune system with bone homeostasis, yet pathologic bone loss is a common sequela associated with autoimmunity and cancer. There are also developmental links, or parallels, between bone and the immune system. Cells that regulate bone turnover share a common precursor with inflammatory immune cells and may restrict themselves anatomically, in part by utilizing a signaling network analo￢gous to lymphocyte costimulation. Efforts are currently under way to further characterize how these two organ systems overlap and to develop therapeutic strategies that benefit from this understanding.

TNF superfamily: Costimulation and clinical applications

Vinay, Dass S.,Kwon, Byoung S. Elsevier 2009 Cell biology international Vol.33 No.4

<P><B>Abstract</B></P><P>The molecules concerned with costimulation belong either to the immunoglobulin (Ig) or tumor necrosis factor (TNF) superfamily. The tumor necrosis superfamily comprises molecules capable of providing both costimulation and cell death. In this review we briefly summarize certain TNF superfamily receptor–ligand pairs that are endowed with costimulatory properties and their importance in health and disease.</P>

Signaling Through the Murine T Cell Receptor Induces IL-17 Production in the Absence of Costimulation, IL-23 or Dendritic Cells

Sarah L. Gaffen,Xikui K. Liu,James L. Clements 한국분자세포생물학회 2005 Molecules and cells Vol.20 No.3

IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. in the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because “costimulation”of T cells through CD28 only mildly enhancedIL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting shortterm production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/

장기이식 면역억제요법의 미래

박재범 대한의사협회 2020 대한의사협회지 Vol.63 No.5

Since the first success of kidney transplantation in 1954, significant advances have been achieved in the field of organ transplantation. It was possible with the introduction of immunosuppressive drugs belonging to the class of calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus, the advances in surgical techniques and perioperative management, the monitoring and management infections, and the highly sensitive and specific antibody detection techniques. Despite recent progress, we currently encounter the limitation of better long-term transplant outcomes mainly because of paradoxical CNI toxicity and failure to control antibody or antibody-mediated rejections. The future direction of immunosuppression can be continued by optimizing immunosuppressive regimens with currently available immunosuppressants for better control of antibodies while avoiding CNI toxicity and by using biological therapeutics such as costimulation blockade agents that provide effective control of antibodies along with a reduction in usage or avoidance of CNIs and may develop as new immunosuppressants in the near future. Moreover, a tolerance induction through transplantation of donor hematopoietic stem cells or an infusion of regulatory cells using various sources of immune cells can also be a promising strategy as it can fundamentally escape from the complications of immunosuppressants. Over and above, it is important to note that the results of clinically applicable immunosuppressants from research in the non-human primate xenotransplantation model at the forefront of the future development of immunosuppressants can be a good opportunity to selectively apply to allo-transplants. No immunosuppressants can be risk-free, and therefore, all new immunosuppressants should be evaluated under the considerations for the risk/benefit ratio in various clinical conditions.

Molecules of the Tumor Necrosis Factor (TNF) Receptor and Ligand Superfamilies: Endless Stories

Kwon, Byung-Suk,Kwon, Byoung-Se The Korea Science and Technology Center 1999 BMB Reports Vol.32 No.5

Tumor necrosis factor (TNF) receptor members have unique structures composed of 2-4 cysteine - rich pseudorepeats in the extracellular domain. On ligation by trimeric ligand molecules, oligomerization of three receptor molecules occurs, which in turn activates the receptor and recruits intracellular signaling molecules to the cytoplasmic tail to initiate biological events. Recently, the numbers of tumor necrosis factor receptor and ligand family members have been rapidly expanding. Functional characterization of the new members has indicated redundant roles with other known members as well as provided insights into novel functions. In particular, identification of soluble decoy receptors which have the ability to bind multiple ligands highlights a complex control mechanism of immune responses by these molecules. Studies of the new members have also revealed that the TNF receptor and ligand family members play an important role in other than the immune system.

Molecules of the Tumor Necrosis Factor (TNF) Receptor and Ligand Superfamilies: Endless Stories

Kwon, Byung-Suk,Kwon, Byoung-Se Korean Society for Biochemistry and Molecular Biol 1999 Journal of biochemistry and molecular biology Vol.32 No.5

Tumor necrosis factor (TNF) receptor members have unique structures composed of 2-4 cysteine - rich pseudorepeats in the extracellular domain. On ligation by trimeric ligand molecules, oligomerization of three receptor molecules occurs, which in turn activates the receptor and recruits intracellular signaling molecules to the cytoplasmic tail to initiate biological events. Recently, the numbers of tumor necrosis factor receptor and ligand family members have been rapidly expanding. Functional characterization of the new members has indicated redundant roles with other known members as well as provided insights into novel functions. In particular, identification of soluble decoy receptors which have the ability to bind multiple ligands highlights a complex control mechanism of immune responses by these molecules. Studies of the new members have also revealed that the TNF receptor and ligand family members play an important role in other than the immune system.