Biomedical subjects

Dennis D Taub

Publications and source records attributed to Dennis D Taub.

At least 19 recordsLinked to original sources

PubMed2006

Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes.

BACKGROUND: Vitamin A (VA) deficiency induces a type 1 cytokine response and exogenously provided retinoids can induce a type 2 cytokine response both in vitro and in vivo. The precise mechanism(s) involved in this phenotypic switch are inconsistent and have been poorly characterized in humans. In an effort to determine if retinoids are capable of inducing Th2 cytokine responses in human T cell cultures, we stimulated human PBMCs with immobilized anti-CD3 mAb in the presence or absence of all-trans retinoic acid (ATRA) or 9-cis-RA. RESULTS: Stimulation of human PBMCs and purified T cells with ATRA and 9-cis-RA increased mRNA and protein levels of IL-4, IL-5, and IL-13 and decreased levels of IFN-gamma, IL-2, IL-12p70 and TNF-alpha upon activation with anti-CD3 and/or anti-CD28 mAbs. These effects were dose-dependent and evident as early as 12 hr post stimulation. Real time RT-PCR analysis revealed a dampened expression of the Th1-associated gene, T-bet, and a time-dependent increase in the mRNA for the Th2-associated genes, GATA-3, c-MAF and STAT6, upon treatment with ATRA. Besides Th1 and Th2 cytokines, a number of additional proinflammatory and regulatory cytokines including several chemokines were also differentially regulated by ATRA treatment. CONCLUSION: These data provide strong evidence for multiple inductive roles for retinoids in the development of human type-2 cytokine responses.

Adult↗

PubMed2006

Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues.

Microarray technology was utilized to isolate disease-specific changes in gene expression by sampling across inferior parietal lobes of patients suffering from late onset AD or non-AD-associated dementia and non-demented controls. Primary focus was placed on understanding how inflammation plays a role in AD pathogenesis. Gene ontology analysis revealed that the most differentially expressed genes related to nervous system development and function and neurological disease followed by genes involved in inflammation and immunological signaling. Pathway analysis also implicated a role for chemokines and their receptors, specifically CXCR4 and CCR3, in AD. Immunohistological analysis revealed that these chemokine receptors are upregulated in AD patients. Western analysis demonstrated an increased activation of PKC, a downstream mediator of chemokine receptor signaling, in the majority of AD patients. A very specific cohort of genes related to amyloid beta accumulation and clearance were found to be significantly altered in AD. The most significantly downregulated gene in this data set was the endothelin converting enzyme 2 (ECE2), implicated in amyloid beta clearance. These data were subsequently confirmed by real-time PCR and Western blot analysis. Together, these findings open up new avenues of investigation and possible therapeutic strategies targeting inflammation and amyloid clearance in AD patients.

Aged↗

PubMed2006

qPrimerDepot: a primer database for quantitative real time PCR.

Gene expression studies employing high throughput real time PCR methods require finding uniform conditions for optimal amplification of multiple targets, often a daunting task. We developed a primer database, qPrimerDepot, which provides optimized primers for all human and mouse RefSeq genes. These primers are designed to amplify desired templates under unified annealing temperature. For most intron-bearing genes, primers flank one of the largest introns thus minimizing background noise due to genomic DNA contamination. The qPrimerDepot database can be accessed at http://primerdepot.nci.nih.gov/ and http://mouseprimerdepot.nci.nih.gov/.

Animals↗

PubMed2006

Ghrelin and the growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility.

Originally thought of as a stomach-derived endocrine peptide acting via its receptors in the central nervous system to stimulate food intake and growth hormone expression, ghrelin and its receptor (growth hormone secretagogue receptor (GHS-R)) are widely expressed in a number of organ systems, including cancer cells. However, the direct functional role of ghrelin and its receptor in tumors of central nervous system origin remains to be defined. Here, we demonstrate that the human astrocytoma cell lines U-118, U-87, CCF-STTG1, and SW1088 express 6-, 11-, 15-, and 29-fold higher levels of GHS-R compared with primary normal human astrocytes. The ligation of GHS-R by ghrelin on these cells resulted in an increase in intracellular calcium mobilization, protein kinase C activation, actin polymerization, matrix metalloproteinase-2 activity, and astrocytoma motility. In addition, ghrelin led to actin polymerization and membrane ruffling on cells, with the specific co-localization of the small GTPase Rac1 with GHS-R on the leading edge of the astrocytoma cells and imparting the tumor cells with a motile phenotype. Disruption of the endogenous ghrelin/GHS-R pathway by RNA interference resulted in diminished motility, matrix metalloproteinase activity, and Rac expression, whereas tumor cells stably overexpressing GHS-R exhibited increased cell motility. The relevance of ghrelin and GHS-R expression was verified in clinically relevant tissues from 20 patients with oligodendrogliomas and grade II-IV astrocytomas. Analysis of a central nervous system tumor tissue microarray revealed that strong GHS-R and ghrelin expression was significantly more common in high grade tumors compared with low grade ones. Together, these findings suggest a novel role for the ghrelin/GHS-R axis in astrocytoma cell migration and invasiveness of cancers of central nervous system origin.

Astrocytoma↗

PubMed2006

CCL5 modulates pneumococcal immunity and carriage.

Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Recently, it has been shown that genetic polymorphisms can result in diminished expression of CCL5, which results in increased susceptibility to and progression of infectious diseases. We show that CCL5, together with Th cytokine mRNA expression, is temporally up-regulated during pneumococcal carriage. To determine the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs before and during Streptococcus pneumoniae strain EF3030-challenge for the initiation of carriage. CCL5 blockade resulted in a decrease of CD4(+) and CD8(+) T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and nasopharyngeal associated lymphoid tissue during the recognition phase of the pneumococcal adaptive immune response. CCL5 blockade significantly reduced the Ag-specific IgG2a and IgG1 Abs in serum and IgA Ab levels in nasal washes. These decreases also corresponded to reductions in Ag-specific T cell (mucosal and systemic) responses. CCL5 inhibition resulted in decreasing the quantity of IL-4- and IFN-gamma-secreting CD4(+) T cells and increasing the number of Ag-specific IL-10-producing CD4(+) T cells; these changes combined also corresponded with the transition from pneumococcal carriage to lethal pneumonia. These data suggest that CCL5 is an essential factor for the induction and maintenance of protective pneumococcal immunity.

Animals↗

PubMed2006

Transient improvement in cognitive function and synaptic plasticity in rats following cancer chemotherapy.

BACKGROUND: Cancer chemotherapy has been associated with cognitive impairment. Several issues complicate such findings including the patients' health, use of multiple chemotherapeutic agents, and proper assessment of cognition. To control these factors, we conducted cognitive studies in female rats receiving cyclophosphamide or 5-fluorouracil (5FU). METHODS: Young (7 months) female Fischer-344 rats received five injections of cyclophosphamide (100 mg/kg), 5FU (150 mg/kg), or saline i.p. every 4 weeks for a total of 18 weeks. Aged (18 months) female Fischer-344 rats were treated with cyclophosphamide (80 mg/kg i.p.) for 16 weeks. After 8 to 10 weeks of recovery, rats were tested in two maze learning tasks, the Morris water maze and the Stone 14-unit T-maze. Neuronal synaptic function was assessed by examining long-term potentiation (LTP) in hippocampal slices obtained from young cyclophosphamide-treated rats. RESULTS: Despite the toxic effects induced by chemotherapy, cyclophosphamide- and 5FU-treated rats showed significantly better maze performance compared with controls. Following 29 to 42 weeks of recovery from chemotherapy, no significant effects were observed on maze performance. In aged rats, cyclophosphamide treatment for 14 weeks also produced toxicity, but no impairment in Stone maze learning after 16 weeks of recovery. When assessed during cyclophosphamide treatment, evidence of impaired LTP emerged; however, with 8 weeks of recovery following five cyclophosphamide treatments, we observed enhanced LTP. CONCLUSION: Despite toxicity accompanying chemotherapy, no evidence of impaired cognitive performance emerged after recovery. Indeed, following 7 to 9 weeks of recovery, we noted evidence of improved learning and LTP.

Age Factors↗

PubMed2005

Ghrelin and immunity: a young player in an old field.

There is increasing evidence of the coupling of immune status to the metabolic system. The communication between the state of systemic and cellular energy balance to immune compartment is mediated via a complex array of cytokines, hormones and neuropeptides. Ghrelin, a recently described orexigenic peptide hormone, is predominantly produced by the stomach and functions as a positive regulator of the somatotropic axis and a peripheral signal of negative energy balance. Apart from its well-studied metabolic effects, ghrelin also exerts multiple regulatory effects on several other organ systems including the cardiovascular, central nervous and immune systems. Here, we summarize the growing evidence of ghrelin as a significant player in the regulation of inflammation and the immune function and the potential therapeutic targeting of ghrelin or its receptor, the growth hormone secretagogue receptor (GHS-R), in various inflammatory and cachexic disease states.

Aging↗

PubMed2005

Relation of plasma leptin to C-reactive protein in older adults (from the Invecchiare nel Chianti study).

Obese subjects have higher circulating levels of C-reactive protein (CRP) than normal subjects, and it has been shown that CRP per se may contribute to atherogenesis. The mechanism linking increased fat mass with high CRP levels has not been exhaustively explained. It has been suggested that adipose tissue-produced cytokines, including interleukin-6, tumor necrosis factor-alpha, and interleukin-1beta, represent the causal link between increased body fat and high CRP levels. It has been hypothesized that the hormone leptin, released by fat cells, may stimulate CRP production independent of cytokines. This study measured circulating leptin, CRP, interleukin-6, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 in 946 community-dwelling older subjects (398 men, 548 women; age range 65 to 102 years) enrolled in a large population-based study. Confounders included demographics, functional, cognitive and affective status, diet and lifestyle, body composition, drugs, and chronic diseases. A direct association was found between leptin and CRP (p = 0.004), independent of cytokines and other possible confounders. The association was stronger in younger than in older subjects but was not influenced by gender or body mass index. In conclusion, these findings suggest that leptin may directly stimulate the production of CRP independent of fat-cell produced cytokines in older adults.

Activities of Daily Living↗

PubMed2005

Insights into thymic aging and regeneration.

The deterioration of the immune system with progressive aging is believed to contribute to morbidity and mortality in elderly humans due to the increased incidence of infection, autoimmunity, and cancer. Dysregulation of T-cell function is thought to play a critical part in these processes. One of the consequences of an aging immune system is the process termed thymic involution, where the thymus undergoes a progressive reduction in size due to profound changes in its anatomy associated with loss of thymic epithelial cells and a decrease in thymopoiesis. This decline in the output of newly developed T cells results in diminished numbers of circulating naive T cells and impaired cell-mediated immunity. A number of theories have been forwarded to explain this 'thymic menopause' including the possible loss of thymic progenitors or epithelial cells, a diminished capacity to rearrange T-cell receptor genes and alterations in the production of growth factors and hormones. Although to date no interventions fully restore thymic function in the aging host, systemic administration of various cytokines and hormones or bone marrow transplantation have resulted in increased thymic activity and T-cell output with age. In this review, we shall examine the current literature on thymic involution and discuss several interventional strategies currently being explored to restore thymic function in elderly subjects.

Adipocytes↗

PubMed2005

Serum erythropoietin and aging: a longitudinal analysis.

OBJECTIVES: To determine the changes in serum erythropoietin with age in patients with and without anemia and to assess the importance of certain comorbidities on changes in erythropoietin level and the development of anemia. DESIGN: Clinical history, hematological parameters, and serum erythropoietin levels were examined at 1- to 2-year intervals for 8 to 30 years. SETTING: Baltimore Longitudinal Study on Aging (BLSA), National Institute on Aging. PARTICIPANTS: One hundred forty-three BLSA participants. MEASUREMENTS: Complete blood count and serum chemistries were performed at the time of each visit, and archived serum samples were used for erythropoietin level. RESULTS: Although all subjects were healthy and without anemia at the time of initial evaluation, some developed chronic illness-most notably hypertension and diabetes mellitus. Erythropoietin levels rose significantly for the group as a whole, and the slope of the rise was found to be greater for those who did not have associated diabetes mellitus or hypertension. During the subsequent years, subjects who developed anemia but did not have hypertension or diabetes mellitus had the greatest slope in erythropoietin rise over time, whereas those with hypertension or diabetes mellitus and anemia had the lowest erythropoietin slope. CONCLUSION: The increase in serum erythropoietin with aging may be compensation for subclinical blood loss, increased red blood cell turnover, or increased erythropoietin resistance of red cell precursors. It is suspected that, with very advanced age, or in those with compromised renal function (e.g., diabetes mellitus or hypertension), the compensatory mechanism becomes inadequate and anemia results.

Adult↗

PubMed2004

Dynamic reorganization of chemokine receptors, cholesterol, lipid rafts, and adhesion molecules to sites of CD4 engagement.

T cell polarization and redistribution of cellular components are critical to processes such as activation, migration, and potentially HIV infection. Here, we investigate the effects of CD4 engagement on the redistribution and localization of chemokine receptors, CXCR4 and CCR5, adhesion molecules, and lipid raft components including cholesterol, GM1, and glycosyl-phosphatidylinositol (GPI)-anchored proteins. We demonstrate that anti-CD4-coated beads (alpha CD4-B) rapidly induce co-capping of chemokine receptors as well as GPI-anchored proteins and adhesion molecules with membrane cholesterol and lipid rafts on human T cell lines and primary T cells to the area of bead-cell contact. This process was dependent on the presence of cellular cholesterol, cytoskeletal reorganization, and lck signaling. Lck-deficient JCaM 1.6 cells failed to cap CXCR4 or lipid rafts to alpha CD4-B. Biochemical analysis reveals that CXCR4 and LFA-1 are recruited to lipid rafts upon CD4 but not CD45 engagement. Furthermore, we also demonstrate T cell capping of both lipid rafts and chemokine receptors at sites of contact with HIV-infected cells, despite the binding of an HIV inhibitory mAb to CXCR4. We conclude that cell surface rearrangements in response to CD4 engagement may serve as a means to enhance cell-to-cell signaling at the immunological synapse and modulate chemokine responsiveness, as well as facilitate HIV entry and expansion by synaptic transmission.

CD4 Antigens↗

PubMed2004

The origins of age-related proinflammatory state.

We hypothesized that the rising levels of inflammatory markers with aging is explained by cardiovascular risk factors and morbidity becoming progressively more prevalent in older persons. Information on inflammatory markers, cardiovascular risk factors, and diseases was collected in 595 men and 748 women sampled from the general population (age, 20-102 years). In both men and women, older age was associated with higher levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRP), and fibrinogen, while soluble IL-6 receptor (sIL-6r) increased significantly with age only in men. Adjusting for cardiovascular risk factors and morbidity, the age regression coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL-18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for cardiovascular morbidity substantially reduced the effect of age on CRP in men but not in women. Findings were confirmed in a subgroup of 51 men and 45 women with low risk profile and no cardiovascular morbidity. Part of the "proinflammatory state" in older persons is related to the high prevalence of cardiovascular risk factor and morbidity.

Adult↗

PubMed2004

Viral macrophage-inflammatory protein-II: a viral chemokine that differentially affects adaptive mucosal immunity compared with its mammalian counterparts.

Chemokines play a profound role in leukocyte trafficking and the development of adaptive immune responses. Perhaps due to their importance in host defense, viruses have adopted many of the hallmarks displayed by chemokines. In particular, viral MIP-II (vMIP-II) is a human chemokine homologue that is encoded by human herpes virus 8. vMIP-II is angiogenic, selectively chemotactic for Th2 lymphocytes, and a homologue of human I-309 and mouse TCA-3, which also differentially attracts Th2 cells. To better understand the effect of viral chemokines on mucosal immunity, we compared the affects of vMIP-II, I-309, and TCA-3 on cellular and humoral immune responses after nasal immunization with OVA. These CCR8 ligands significantly enhanced Ag-specific serum and mucosal Abs through increasing Th2 cytokine secretion by CD4+ T cells. These alterations in adaptive humoral and cellular responses were preceded (12 h after immunization) by an increase in CD4+ T and B cells in nasal tracts with decreases of these leukocyte populations in the lung. Interestingly, vMIP-II increased neutrophil infiltration in the lung and Ag-specific IL-10-secreting CD4+ T cells after immunization. Although I-309 increased the number of CD28-, CD40L-, and CD30-positive, Ag-stimulated naive CD4+ T cells, vMIP-II and TCA-3 decreased the number of CD28-, CD40L-, and CD30-positive, resting naive CD4+ T cells. Taken together, these studies suggest that CCR8 ligands direct host Th2 responses, and vMIP-II up-regulates IL-10 responses and limits costimulatory molecule expression to mitigate host immunity.

Adjuvants, Immunologic↗

PubMed2004

Anomalous expression of the HLA-DR alpha and beta chains in ovarian and other cancers.

Tumor formation in immunocompetent hosts is believed to be dependent on the ability of tumor cells to evade the immune system, as suggested by the alterations of expression of the major histocompatibility complex (MHC) and related molecules in a number of cancers. Our previous serial analysis of gene expression (SAGE) study revealed that HLA-DRA (encoding the alpha chain of HLA-DR) is one of the most highly overexpressed genes in ovarian cancer. This finding was unanticipated, as overexpression of MHC molecules would be expected to increase tumor immunogenicity, therefore compromising tumor growth. We have now examined the expression of HLA-DR alpha chain in ovarian and a variety of other cancers using tissue arrays and found it overexpressed in a majority of the cancer tissues investigated. In contrast, the HLA-DR beta chain, which together with the alpha chain forms the functional HLA-DR complex, was not frequently found expressed in cancer, resulting to a lack of mature HLA-DR in these tissues. Interestingly, HLADRA and HLADRB transcripts were both found expressed in many other cancer types, including ovarian cancer, suggesting that the downregulation of HLADR beta chain is a post-transcriptional or post-translational mechanism. In addition, we observed high levels of the invariant chain (Ii/CD74) expression in both the cytoplasm and plasma membrane of ovarian tumor cells, possibly contributing to the lack of mature HLA-DR protein expression. Interestingly, we found that IFN-gamma could induce mature HLA-DR at the surface of normal ovarian cells, while this ability was reduced in tumor cells. Together, these data suggest that, while ovarian tumors overexpress HLA-DR alpha, perhaps as a result of inflammatory events in the tumor microenvironment, the tumor cells may have compensatory mechanisms to reduce the production of functional MHC class II molecules, thus reducing immunogenicity and favoring tumor growth. In addition, because of its ubiquitous expression in ovarian and other cancers, HLA-DR alpha may represent a novel biomarker for malignancy.

Adenocarcinoma, Clear Cell↗

PubMed2004

Age-associated alterations in CXCL1 chemokine expression by murine B cells.

BACKGROUND: The CXCL1 chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), have been shown to play a role in a number of pathophysiological disease states including endotoxin-induced inflammation and bacterial meningitis. While the expression of these chemokines has been identified in a variety of cell types in the mouse, little is known about their expression with murine B-lymphocytes. RESULTS: Here, we demonstrate that highly purified murine splenic B cells are capable of expressing both MIP-2 and KC protein and mRNA upon activation with lipopolysaccharide (LPS) but not in response to anti-micro and anti-CD40 in combination with interleukin-4 (IL-4) stimulation. Moreover, these chemokines are expressed at higher levels in B cells derived from young (4 m) compared to old (24-29 m) mice. Upon fractionation into distinct B-cell subsets, we found that the expression of MIP-2 and KC by aged follicular (FO) B cells is significantly decreased when compared to the same cells from younger mice, while only MIP-2 production was found to be diminished in aged marginal zone (MZ) B cells. Interestingly, MIP-2 and KC production by newly formed (NF) B cells did not significantly differ with age. Moreover, the potential relevance of these findings is supported by the poor ability of LPS-activated aged B cells to specifically mediate CXCL1-dependent leukocyte recruitment when compared to younger B cells. CONCLUSION: Overall, the decreased expression of CXCL1 chemokines by aged B cells in response to LPS may have potential implications on the secondary recruitment of leukocytes to sites of microbial infections and inflammation possibly contributing to the increased susceptibility of older subjects to pathogen challenge.

Aging↗

PubMed2004

Quantitative differences in lipid raft components between murine CD4+ and CD8+ T cells.

BACKGROUND: Lipid rafts have been shown to play a role in T cell maturation, activation as well as in the formation of immunological synapses in CD4+ helper and CD8+ cytotoxic T cells. However, the differential expression of lipid raft components between CD4+ and CD8+ T cells is still poorly defined. To examine this question, we analyzed the expression of GM1 in T cells from young and aged mice as well as the expression of the glycosylphosphatidylinositol (GPI)-linked protein Thy-1 and cholesterol in murine CD4+ and CD8+ T cell subpopulations. RESULTS: We found that CD4+CD8- and CD8+CD4- thymocytes at different stages of maturation display distinct GM1 surface expression. This phenomenon did not change with progressive aging, as these findings were consistent over the lifespan of the mouse. In the periphery, CD8+ T cells express significantly higher levels of GM1 than CD4+ T cells. In addition, we observed that GM1 levels increase over aging on CD8+ T cells but not in CD4+ T cells. We also verified that naïve (CD44lo) and memory (CD44hi) CD8+ T cells as well as naïve and memory CD4+ T cells express similar levels of GM1 on their surface. Furthermore, we found that CD8+ T cells express higher levels of the GPI-anchored cell surface protein Thy-1 associated with lipid raft domains as compared to CD4+ T cells. Finally, we observed higher levels of total cellular cholesterol in CD8+ T cells than CD4+ T cells. CONCLUSION: These results demonstrate heterogeneity of lipid raft components between CD4+ and CD8+ T cells in young and aged mice. Such differences in lipid raft composition may contribute to the differential CD4 and CD8 molecule signaling pathways as well as possibly to the effector responses mediated by these T cell subsets following TCR activation.

Aging↗

PubMed2004

Alterations in mast cell function and survival following in vitro infection with human immunodeficiency viruses-1 through CXCR4.

HIV-1 infection leads to a disease that attacks the central regulatory mechanisms of the immune response. As mucosal tissue is one of the primary sites infected with HIV in vivo, we examined the effects of HIV exposure on human mast cells, important components of mucosal defense. Using the human mast cell line, HMC-1, which expresses CXCR4 but not CCR5 on the cell surface, we found that several HIV-1 X4 tropic lab (IIIB, RF) and primary isolates but not R5 (BAL, ADA) isolates productively infected these cells. Furthermore, stem cell factor-dependent mast cells derived from primary fetal liver or cord blood cultures were also productively infected with both X4 and R5 HIV-1 strains. Infection was blocked at the level of viral entry using monoclonal antibodies to CXCR4 and CD4. Treatment of HMC-1 with TNF-alpha and TGF-beta stimulated cell surface expression of CCR5 and up-regulated expression of both CCR5 and CXCR4 on primary mast cells, leading to increased susceptibility to both X4 and R5 viral isolates. HIV-1 infection also resulted in histamine release from these mast cells, most due in part to HIV-mediated cell death. These results demonstrate that X4 viruses can use CD4 and the CXCR4 receptor to infect mast cells, suggesting that mast cell-T cell interactions may contribute to HIV mediated immune dysfunction in the mucosa.

Apoptosis↗

PubMed2004

The immunoregulatory effects of homocysteine and its intermediates on T-lymphocyte function.

Elevated levels of homocysteine (Hcy) have been identified as independent risk identifiers for cardiovascular disease, cerebrovascular disease as well as for all-cause mortality. Despite the potential importance of these observations, a definitive pathological role for Hcy or its various metabolites in any of these conditions has not been established. Particularly deficient is a description of the effects of elevated levels of homocysteine on immune function. Folic acid and vitamin B12 deficiency have been independently associated with decreased immune function, the apoptosis of bone marrow hematopoietic progenitor cells and the appearance of leukocytes with hypomethylated DNA in the peripheral circulation. A specific role for Hcy or its metabolites in these processes has not been described. We have examined the effects of Hcy and its various derivatives on T cell activation, differentiation and cell viability. Our results have demonstrated that Hcy is a potent concentration-dependent T cell activator promoting cellular activation and differentiation as well as potentiating activation-induced cell death (AICD) and cellular apoptosis. Overall, Hcy appears to exert diverse effects on immune function in the circulation and within the tissue microenvironment possibly contributing to age-related immune dysfunction and disease pathology.

Aged↗