Biomedical subjects

J T Tan

Publications and source records attributed to J T Tan.

11 recordsLinked to original sources

PubMed2006

T cell memory.

T cell memory induced by prior infection or vaccination provides enhanced protection against subsequent microbial infections. The processes involved in generating and maintaining T cell memory are becoming better understood due to recent technological advances in identifying memory T cells and monitoring their behavior and function in vivo. Memory T cells develop in response to a progressive set of cues-starting with signals from antigen-loaded, activated antigen-presenting cells (APCs) and inflammatory mediators induced by the innate immune response, to the poorly defined subsequent signals triggered as the immune response wanes toward homeostasis. The persistence of the resting memory T cells that eventually develop is regulated by cytokines. This chapter discusses recent findings on how memory T cells develop to confer long-term protective immunity.

Animals↗

PubMed2001

Characterization of virus-mediated inhibition of mixed chimerism and allospecific tolerance.

Simultaneous blockade of the CD28 and CD40 T cell costimulatory pathways has been shown to effectively promote skin allograft survival in mice. Furthermore, blockade of one or both of these pathways has played a central role in the development of strategies to induce mixed hematopoietic chimerism and allospecific tolerance. It has recently been observed that the beneficial effects of CD40 blockade and donor splenocytes in prolonging skin graft survival can be abrogated by some viral infections, including lymphocytic choriomeningitis virus (LCMV). In this study, we show that LCMV infection prevents prolonged allograft survival following CD28/CD40 combined blockade. We further show that LCMV prevents the induction of allospecific tolerance and mixed hematopoietic chimerism, while delay of infection for 3-4 wk posttransplant has no effect on tolerance induction. Because of reports of anti-H-2(d) activity following LCMV infection, we assayed the ability of LCMV-specific T cells to respond to alloantigen at a single cell level. Although we confirm that LCMV infection induces the generation of alloreactive cells, we also demonstrate that LCMV-specific T cells do not divide in response to alloantigen. The alloresponse suppressed by costimulation blockade is restored by LCMV infection and correlates with increased dendritic cell maturation. We hypothesize that the costimulation blockade-resistant rejection mediated by LCMV could be partly attributable to the up-regulation of alternative costimulatory pathways subsequent to LCMV-induced dendritic cell maturation.

Animals↗

PubMed2001

IL-7 is critical for homeostatic proliferation and survival of naive T cells.

In T cell-deficient conditions, naive T cells undergo spontaneous "homeostatic" proliferation in response to contact with self-MHC/peptide ligands. With the aid of an in vitro system, we show here that homeostatic proliferation is also cytokine-dependent. The cytokines IL-4, IL-7, and IL-15 enhanced homeostatic proliferation of naive T cells in vitro. Of these cytokines, only IL-7 was found to be critical; thus, naive T cells underwent homeostatic proliferation in IL-4(-) and IL-15(-) hosts but proliferated minimally in IL-7(-) hosts. In addition to homeostatic proliferation, the prolonged survival of naive T cells requires IL-7. Thus, naïve T cells disappeared gradually over a 1-month period upon adoptive transfer into IL-7(-) hosts. These findings indicate that naive T cells depend on IL-7 for survival and homeostatic proliferation.

Animals↗

PubMed2000

A zebrafish vitellogenin gene (vg3) encodes a novel vitellogenin without a phosvitin domain and may represent a primitive vertebrate vitellogenin gene.

By analysis of zebrafish EST (expressed sequence tag) clones from an adult cDNA library, we have identified 44 clones, about 11% of the adult EST clones, encoding vitellogenins. These vitellogenin EST clones have been derived from at least seven distinct vitellogenin genes. One of the largest vitellogenin cDNA clones, vg3, and its 5' extended clone isolated by 5' RACE (rapid amplification of cDNA ends)-PCR, have been sequenced completely. The deduced complete sequence includes a predicted mature vitellogenin of 1233 amino acids and a truncated signal peptide of 18 amino acids. Interestingly, the predicted vitellogenin has no polyserine phosvitin domain. The lack of the phosvitin domain was confirmed by isolation and sequencing of the vg3 genomic region. Phylogenetic analysis indicates that the phosvitinless vitellogenin is an intermediate between invertebrate vitellogenins and all known vertebrate vitellogenins, and thus may represent a primitive vertebrate vitellogenin. Like other vitellogenins in vertebrates, the phosvitinless vitellogenin is also synthesized mainly in the liver and weakly in the intestine.

Amino Acid Sequence↗

PubMed2000

Analysis of expression and function of the costimulatory molecule 4-1BB in alloimmune responses.

BACKGROUND: 4-1BB (CD137) is a T cell costimulatory molecule that promotes T cell activation. In this study, we investigated the role of 4-1BB costimulation in allogeneic T cell responses. METHODS: Vascularized heart transplantation, allogeneic mixed leukocyte reaction (MLR), and graft versus host disease models were used to examine 4-1BB and 4-1BBL expression. In addition, agonistic anti-4-1BB antibodies were used in MLR to functionally analyze T cell responses. RESULTS: Using a heart transplant model, we found that 4-1BB and 4-1BBL transcripts were both expressed in rejecting cardiac grafts. In the allogeneic MLR, 4-1BB was expressed on both activated CD4 and CD8 T cells and 4-1BB was expressed on T cells after multiple cell divisions in vivo. Functionally, 4-1BB was a potent stimulator of proliferation, cytokine secretion, and CD25 expression by CD8 T cells, but 4-1BB signals had a weak effect on the proliferation of CD4 T cells. Because 4-1BB promoted the secretion of IL-2 and the expression of CD25 on CD8 T cells, we investigated whether IL-2 was the only factor whereby 4-1BB signals induced CD8 T cell proliferation. Although IL-2 was required for optimal CD8 T cell proliferation, 4-1BB also costimulated CD8 T cell proliferation independently of IL-2. CONCLUSIONS: This study demonstrates that 4-1BB is expressed on activated, maximally divided T cells and shows that 4-1BB promotes CD8 T cell proliferation by enhancing signals through the IL-2 receptor and by other mechanisms independent of the IL-2 pathway.

Animals↗

PubMed2000

4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination.

Peptide vaccination induces T cell activation and cytotoxic T cell development. In an effort to understand what factors can improve immune responses to peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since 4-1BB has been shown to promote T cell responses in other systems. 4-1BBL-deficient (-/-) and wild-type (+/+) mice were immunized with a lipidated lymphocytic choriomeningitis virus (LCMV) peptide NP396-404. Analysis of peptide-specific responses early after immunization by CTL assay, intracellular IFN-gamma staining, and IFN-gamma enzyme-linked immunospot assay (ELISPOT) indicated that CD8 T cell responses were reduced 3- to 10-fold in the absence of 4-1BB costimulation. Moreover, when agonistic anti-4-1BB Ab was given, CD8 T cell responses in 4-1BBL-/- mice were augmented to levels similar to those in 4-1BBL+/+ mice. Two months after immunization, 4-1BBL+/+ mice still had epitope-specific cells and were protected against viral challenge, demonstrating that peptide vaccination can induce long-term protection. In fact, 70% of CD8 T cells were specific for the immunizing peptide after viral challenge, demonstrating that strong, epitope-specific CD8 T cell responses are generated after peptide vaccination. In contrast, peptide-immunized 4-1BBL-/- mice had fewer epitope-specific cells and were impaired in their ability to resolve the infection. These results show that immunization with a single LCMV peptide provides long term protection against LCMV infection and point to costimulatory molecules such as 4-1BB as important components for generating protective immunity after vaccination.

Animals↗

PubMed1999

4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses.

4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L-/-) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions.

4-1BB Ligand↗

PubMed1999

Expression of a zebrafish iroquois homeobox gene, Ziro3, in the midline axial structures and central nervous system.

We describe a zebrafish gene, Ziro3, which is highly homologous to Xenopus and mouse iroquois3. Ziro3 expression starts during gastrulation in the dorsal axial mesoderm that develops into the notochord. Later, the expression is limited to the chordo-neural hinge in the tailbud. Ziro3 expression also occurs in the central nervous system (CNS), excluding the telencephalon. The level of Ziro3 expression differs in odd and even rhombomeres. In the midbrain-hindbrain boundary (MHB) and rhombomere 6, Ziro3 transcripts appear only after the formation of the cerebellum and otic vesicle, respectively.

Amino Acid Sequence↗

PubMed1998

Regulation of leptin expression and secretion by corticosteroids and insulin. Implications for body weight.

Leptin is an important hormone that has potent effects on appetite and body weight. The regulation of leptin gene expression and secretion by corticosteroids and insulin was studied in the rat. Adrenalectomy resulted in a significant reduction in leptin gene expression and secretion. The reduction was corrected by hormonal replacement with corticosterone pellets, showing that normal levels of circulating corticosteroids are required to maintain leptin expression and secretion in the body. Chronic treatment with dexamethasone (DEX) over 3 wk did not significantly increase leptin gene expression and secretion, contrary to earlier reports using shorter treatment paradigms. The profound weight loss associated with chronic DEX treatment may have abrogated the direct stimulatory effect of DEX on leptin gene expression and secretion, indicating a possible crosstalk between corticosteroids and leptin in the regulation of body weight. Shorter-term treatment of animals with DEX (3.7 micrograms/g body wt; 24 h) increased leptin gene expression and secretion about 2-fold and 1.4-fold, respectively. The increase was independent of circulating insulin concentrations. In streptozotocin-treated rats, short-term DEX treatment increased leptin gene expression and secretion about 3.5-fold and 2-fold, respectively. The data indicate that circulating leptin concentrations and adipose tissue leptin expression are dependent on corticosteroids and insulin. Although acute DEX treatment resulted in a stimulatory effect on leptin secretion and expression, chronic DEX treatment did not. The stimulatory effect of DEX on leptin is independent of circulating insulin concentrations.

Adipose Tissue↗

PubMed1993

Will patients with contact lens problems accept excimer laser photorefractive keratectomy?

One hundred six patients who presented to the Singapore National Eye Centre with contact lens related problems from June 1992 to September 1992 were given information about photorefractive keratectomy (PRK) and asked to give their reactions to the procedure. The patients in the study were largely female myopes (89%) with diverse contact lens problems. Forty-seven of 106 patients (44%) indicated they would consider PRK for themselves. Asked why, 37 patients (79%) cited the convenience of not needing spectacles or contact lenses. Of the 59 patients (56%) who were not interested in PRK, 46 patients (78%) expressed fears about possible complications; others were not convinced of the efficacy of PRK. The group of patients interested in PRK was comprised of more males (P = 0.0099) and more high myopes (P = 0.036). Of the 47 patients keen on PRK, 38 patients fit the surgical criteria. At 3 months after conclusion of the study, only two patients had undergone PRK.

Adolescent↗

PubMed1989

Contact lens complications: the Singapore experience.

An analysis of all cases presenting with contact lens related complications to the Department of Ophthalmology, Singapore General Hospital, was undertaken over a period of one year (October 1987 to September 1988). A total of 147 patients were seen with contact lens related problems. The overall incidence of patients with contact lens related problems was 0.8% of all referrals to the Department of Ophthalmology during this period. This survey was done in a prospective manner and an analysis with regard to age, sex distribution, presenting complaints, sterilisation technique and diagnoses was done. The study showed a significantly higher incidence of serious sight-threatening complications in extended wear lens wearers. Hard contact lens and Hard Gas Permeable lens wearers had no serious complications seen. There was a significant number of young adults choosing to wear the extended wear contact lens for the convenience of not having to clean their lenses daily even though they had a higher risk of a sight-threatening complication. Interviews with the patients also showed a universally poor knowledge of contact lens hygiene.

Adolescent↗