Interaction Of T-lymphocytes Research Articles

T-Lymphocyte Interactions with the Neurovascular Unit: Implications in Intracerebral Hemorrhage.

In the pathophysiology of hemorrhagic stroke, the perturbation of the neurovascular unit (NVU), a functional group of the microvascular and brain intrinsic cellular components, is implicated in the progression of secondary injury and partially informs the ultimate patient outcome. Given the broad NVU functions in maintaining healthy brain homeostasis through its maintenance of nutrients and energy substrates, partitioning central and peripheral immune components, and expulsion of protein and metabolic waste, intracerebral hemorrhage (ICH)-induced dysregulation of the NVU directly contributes to numerous destructive processes in the post-stroke sequelae. In ICH, the damaged NVU precipitates the emergence and evolution of perihematomal edema as well as the breakdown of the blood–brain barrier structural coherence and function, which are critical facets during secondary ICH injury. As a gateway to the central nervous system, the NVU is among the first components to interact with the peripheral immune cells mobilized toward the injured brain. The release of signaling molecules and direct cellular contact between NVU cells and infiltrating leukocytes is a factor in the dysregulation of NVU functions and further adds to the acute neuroinflammatory environment of the ICH brain. Thus, the interactions between the NVU and immune cells, and their reverberating consequences, are an area of increasing research interest for understanding the complex pathophysiology of post-stroke injury. This review focuses on the interactions of T-lymphocytes, a major cell of the adaptive immunity with expansive effector function, with the NVU in the context of ICH. In cataloging the relevant clinical and experimental studies highlighting the synergistic actions of T-lymphocytes and the NVU in ICH injury, this review aimed to feature emergent knowledge of T cells in the hemorrhagic brain and their diverse involvement with the neurovascular unit in this disease.

Modeling of tumor response to macrophage and T lymphocyte interactions in the liver metastatic microenvironment.

The dynamic interactions between macrophages and T-lymphocytes in the tumor microenvironment exert both antagonistic and synergistic functions affecting tumor growth. Extensive experimental effort has been expended to investigate immunotherapeutic strategies targeting macrophage polarization as well as T-cell activation with the goal to promote tumor cell killing and cancer elimination. However, these interactions remain poorly understood, and cancer immunotherapeutic strategies are often disappointing. The complex system encompassing innate and adaptive immune cell activity in response to tumor growth could benefit from a systems perspective built upon mathematical modeling. This study develops a modeling system to help evaluate the effects of macrophage and T-lymphocyte interactions on tumor growth. The system enables simulating the combined cytotoxic and tumor-promoting interactions of these two immune cell populations in a vascularized organ microenvironment, such as in liver metastases. A hypothetical immunotherapeutic strategy is simulated to increase the number of tumor-suppressive (M1-phenotype) vs. tumor-promoting (M2-phenotype) macrophages to gauge their effects on CD8+ T-cells and CD4+ T-helper cells, which in turn affect the macrophage functions. The results highlight the dynamic interactions between macrophages and T-lymphocytes in the tumor microenvironment and show that with the chosen set of parameter values, the overall cytotoxic effect from macrophages and T-lymphocytes obtained by driving the M1:M2 ratio higher could saturate and fail to achieve tumor regression. Further expansion of this modeling platform to include additional tumor-immune cell interactions, coupled with parameters representing particular tumor characteristics, could enable systematic evaluation of immunotherapeutic strategies tailored to patient-tumor specific conditions, including metastatic disease.

Serum and tissue angiotensin-converting enzyme in patients with alopecia areata.

Alopecia areata is an immune-dependent disorder characterized by the interaction of T-lymphocytes with follicular antigens. Recent studies have shown the existence of a local renin-angiotensin system in the skin, where angiotensin-converting enzyme (ACE) plays a role in autoimmunity and inflammation. The objective of this study was to evaluate serum and tissue ACE activity in patients with alopecia areata. This case-control study was conducted on patients with alopecia areata and healthy controls. Serum and tissue ACE activity were assessed and compared between the two groups. Twenty-five alopecia areata patients (60% male, mean age 32.1 ± 9.9 years) and 24 controls (50% male, mean age 37.4 ± 8.8 years) were included. Mean serum ACE activity was 52.1 ± 9 U/L in cases and 55.3 ± 14.7 U/L in controls (P = 0.37). Tissue ACE activity was significantly lower in cases in all parts of the skin i.e. epidermis (P = 0.016), follicular epithelium (P = 0.004), and endothelium (P = 0.037). Among cases, serum ACE activity was significantly higher in patients with more severe disease (P = 0.030), nonpatchy alopecia areata (alopecia universalis; ophiasis, patchy and ophiasis, diffuse) (P = 0.029), and with nail involvement (P = 0.027). The sample size was too small to draw definite conclusions. Further, most of the patients had only mild or moderate alopecia areata. Unlike in some other inflammatory diseases, the tissue level of ACE seems to be significantly lower in alopecia areata compared to normal controls. Serum ACE was significantly higher in patients with more severe disease.

Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy

Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy

Early Murine T-lymphocyte Activation Is Accompanied by a Switch from N-Glycolyl- to N-Acetyl-neuraminic Acid and Generation of Ligands for Siglec-E

It is well established that murine T-lymphocyte activation is accompanied by major changes in cell-surface sialylation, potentially influencing interactions with sialic acid-binding immunoglobulin-like lectins (siglecs). In the present study, we analyzed early activation of murine CD4+ and CD8+ T-lymphocytes at 24 h. We observed a striking and selective up-regulation in the binding of a recombinant soluble form of siglec-E, an inhibitory siglec, which is expressed on several myeloid cell types including antigen-presenting dendritic cells. In contrast, much lower levels of T cell binding were observed with other siglecs, including sialoadhesin, CD22, and siglec-F and the plant lectins Maackia amurensis leukoagglutinin and Sambucus nigra agglutinin. By mass spectrometry, the sialic acid content of 24-h-activated CD4+ and CD8+ T-lymphocytes exhibited an increased proportion of N-acetyl-neuraminic acid (NeuAc) to N-glycolyl-neuraminic acid (NeuGc) in N-glycans. Reduced levels of NeuGc on the surface of activated T cells were demonstrated using an antibody specific for NeuGc and the expression levels of the gene encoding NeuAc- to NeuGc-converting enzyme, CMP-NeuAc hydroxylase, were also reduced. Siglec-E bound a wide range of sialylated structures in glycan arrays, had a preference for NeuAc versus NeuGc-terminated sequences and could recognize a set of sialoglycoproteins that included CD45, in lysates from activated T-lymphocytes. Collectively, these results show that early in T cell activation, glycan remodelling involves a switch from NeuGc- to NeuAc-terminating oligosaccharides on cell surface glycoproteins. This is associated with a strong up-regulation of siglec-E ligands, which may be important in promoting cellular interactions between early activated T-lymphocytes and myeloid cells expressing this inhibitory receptor.

Analysis of Peptide/MHC-Induced TCR Downregulation: Deciphering the Triggering Kinetics

The interaction of T-lymphocytes with antigen-presenting cells displaying a small number of specific peptide/major histocompatibility complexes results in the downregulation of a large number of T-cell receptors (TCR), suggesting serial TCR triggering. However, the details of TCR downregulation are controversial. In particular, the level of comodulation of nonengaged TCR reported by different authors ranges from essentially none to considerable levels. Here, we address this controversy using complementary experimental and mathematical techniques. We find that TCR downregulation is very rapid during the first 2-4 min after T-cell antigen-presenting cells contact formation. After this phase, TCR downregulation proceeds at a relatively slow rate. Statistical and computational analyses show that this pronounced change in downregulation kinetics is compatible with the notion of initial serial triggering of clustered TCR followed by serial triggering of individual TCR. We further propose a compatible mechanism for concurrent triggering of multiple TCR by a single peptide/major histocompatibility complex. We provide a unified picture of productive TCR engagement and downregulation in which TCR triggering characteristics evolve from an initial cooperative phase to a sustained phase of signal accumulation.

Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa

It has recently been suggested that C-C chemokines may play a role in the organ-specific homing of lymphocytes, but there is not enough in vivo evidence in intestinal mucosa. The aim of this study was to examine whether thymus-expressed chemokine (TECK)/CCL25 and its ligand CCR9 are involved in T-lymphocyte interaction with microvessels of murine intestinal mucosa. T lymphocytes from the small intestine were fluorescence labeled, and their adhesion to mucosal microvessels was observed by intravital microscopy. Lamina proprial lymphocytes (LPL) and intraepithelial lymphocytes (IEL) adhered to both the small intestine and colon, and desensitization of CCR9 with TECK/CCL25 or anti-TECK/CCL25 antibody significantly inhibited these adhesions only in small intestine. At both sites, TNF-alpha significantly increased LPL adhesion but not IEL adhesion. Desensitization of CCR9 or anti-TECK/CCL25 antibody also attenuated the TNF-alpha-induced LPL adhesion in the small intestine. Increased expression of TECK/CCL25 by TNF-alpha was observed in the lamina propria of small intestine. TECK/CCL25 may thus play an important role in the adherence of mucosal lymphocytes to the microvessels of the small intestine but not the colon under uninflamed as well as inflamed conditions.

Cytokine-inducible CD40 gene expression in vascular smooth muscle cells is mediated by nuclear factor κB and signal transducer and activato of transcription-1

The interaction of T-lymphocytes expressing the CD40 ligand (CD154) and cells of the vessel wall expressing the corresponding receptor protein (CD40) may play an important role in chronic inflammation including arteriosclerosis. One way of interfering with CD40-CD154 signalling is to prevent CD40 expression, the regulation of which, however, has yet to be elucidated. Therefore, we studied CD40 expression in rat aortic cultured smooth muscle cells. Both CD40 mRNA and protein expression in these cells was markedly enhanced as early as 6 h after exposure to different pro-inflammatory cytokines. Experiments with actinomycin D and subsequent run-on analyses revealed that CD40 expression in response to these cytokines was regulated at the level of transcription. Moreover, electrophoretic mobility shift analyses along with the employment of transcription factor decoy oligodeoxynucleotides demonstrated that tumor necrosis factor α via nuclear κB and interferon-γ via signal transducer and activator of transcription-1 up-regulate CD40 gene expression in rat aortic cultured smooth muscle cells.

T-Lymphocyte Interactions With Endothelium and Extracellular Matrix

T-lymphocyte movement out of the bloodstream and into tissue is critical to the success of these cells in their role in immunosurveillance. This process involves interactions of the T-cell with endothelium as well as with extracellular matrix. Central to these interactions are a number of T-cell adhesion molecules and their endothelial and extracellular matrix ligands. The identification and functional characterization of adhesion molecules have been the subject of intensive research in recent years. We highlight here the latest developments in this rapidly expanding field as they pertain to T-cell interactions with endothelial cells and extracellular matrix components, including: (1) identification of adhesion molecule families, including the selectins, mucins, integrins, immunoglobulin superfamily members, and cadherins; (2) elucidation of the multi-step adhesion cascade that mediates the rolling, arrest, and eventual diapedesis of T-cells through the vascular endothelium into the surrounding tissue; (3) the changes in adhesion molecule expression that accompany T-cell maturation and activation, and the impact of those changes on T-cell migration; (4) the functional relevance of the extracellular matrix for T-cell function; and (5) the clinical relevance of adhesion molecules and the potential for targeting these molecules for the amelioration of immune-mediated diseases.

BRONCHIOLITIS ASSOCIATED WITH BONE MARROW TRANSPLANTATION

New onset airflow obstruction after BMT is a relatively common complication and may be seen in as many as 11% of long-term survivors of allogeneic BMT with chronic GVHD. Bronchiolitis and, occasionally, obliterative bronchiolitis is seen in the majority of cases in which histopathology is available. The primary risk factors recognized are the presence of clinical chronic GVHD, administration of methotrexate as an immunosuppressive, and older recipient age. Improved control of chronic GVHD with effective agents such as cyclosporine likely will decrease the incidence of this airway disorder. The causes probably are multifactorial and donor cytotoxic T-lymphocyte interaction with host cells is a likely contributor in many cases. The clinical course is variable, but the process usually is fatal in cases with rapidly progressive or severe obstruction. Interventions are directed at immune suppression and at diagnosing and treating infections that frequently occur in association with the airflow obstruction.

The nature of allorecognition

Understanding the nature of allorecognition is fundamental to the design of antigen-specific therapies for transplantation. As recently as 10 years ago it was generally believed that recognition of major histocompatibility complex (MHC) molecules by T lymphocytes was direct and represented the "simplest" kind of T-lymphocyte interaction. It is now clear that the nature of allorecognition is complex, involving a variety of different forms of MHC antigens with or without peptides contained in their antigen-binding groove. In addition, there is renewed interest in alternative forms of allorecognition, including so-called indirect allorecognition, in which donor alloantigens are recognized as peptides in the context of recipient self. Lastly, it appears that cells other than T lymphocytes, eg, natural killer cells, are capable of antigen-specific recognition and may be responsible for heretofore underappreciated mechanisms of transplant rejection.

Activated T-cell adhesion to thrombospondin is mediated by the alpha 4 beta 1 (VLA-4) and alpha 5 beta 1 (VLA-5) integrins.

T lymphocytes utilize adhesion receptors in a regulated manner to interact with other cells and with components of the extracellular matrix. These cell-cell and cell-matrix interactions serve a critical role in T cell recognition of foreign Ag and in the migration of T cells to various anatomic sites in vivo. Thrombospondin is an extracellular matrix protein that is transiently expressed at high concentration in damaged and inflamed tissue. Given recent evidence implicating a role for the extracellular matrix in modulating T-cell migration and function, we analyzed T-lymphocyte interactions with thrombospondin. We show here that CD4+ T cells specifically adhere to thrombospondin predominantly via the 70 kDa core region of the thrombospondin molecule. Antibody blocking and affinity chromatography analysis suggest that T-cell adhesion to thrombospondin involves three distinct receptors: an activation-independent receptor that mediates adhesion of resting T cells, and the alpha 4 beta 1 and alpha 5 beta 1 integrins, which mediate a rapid increase in adhesion to thrombospondin upon activation. These three molecules appear to be novel thrombospondin receptors, as other receptors previously implicated in the adhesion of nonlymphoid cells to thrombospondin appear not to be involved in T-cell/thrombospondin interactions. The up-regulation of alpha 4 beta 1 and alpha 5 beta 1 functional activity upon activation is associated with the preferential adhesion of memory T cells to thrombospondin. Our results thus define three novel thrombospondin receptors, and provide additional evidence that extracellular matrix proteins play an important role in lymphocyte migration into, and retention in, inflammatory sites.

Infectious agents in reactive arthritis

It is now clear that the deposition and persistence of bacterial antigens in the joint are significant features of reactive arthritis. It is possible that in some instances this represents persistence of live bacteria, and several studies point to the potential value of antimicrobial therapy. Searches for bacterial DNA and RNA have yielded conflicting data, however, so further developments in this area will be of great importance. It is likely that bacterial antigens interact in some way with class I major histocompatibility complex (MHC) antigens in the pathogenesis of reactive arthritis. However, with the increasing understanding of the structure and function of HLA molecules, some evidence of a classic antigen-class I MHC-CD8 T-lymphocyte interaction is now emerging. Thus far, the mechanisms that link HLA-B27 and bacterial antigens with reactive arthritis remain unclear.

T-lymphocyte interactions in cardiac transplant rejection

Transplant rejection is a complex cascade of cellular and molecular inflammatory events triggered by the recognition of donor antigens by the recipient immune system. The interaction between T-cell receptors on “helper” T cells and donor antigen confers specificity of the response, whereas accessory cell interactions and growth factor (lymphokine) secretion regulate the variety of cellular responses. An understanding of these cellular and molecular interactions may promote new therapeutic strategies.

Modulation of glomerular mesangial cell growth and prostaglandin release by T-lymphocyte products

Mesangio-proliferative and crescentic forms of glomerulonephritis (GN) are eharacterised by an initial influx of T-lymphocytes into the glomerulus [1]. This was shown not only for animal models of GN, but also for human GN. The participating lymphocytes mainly represent activated T-helper cells. A recent investigation from our laboratory showed that recombinant T-lymphocyte factors are able to induce class II major histocompatibility antigens in intrinsic rat mesangial cells (MC) [3]. In this study we show that there are specific interactions between growing mesangial cells and syngeueic, activated T-lymphocytes in co-culture, which could be reproduced by recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) not only with mouse but also with human MC. These data indicate a direct interaction of T-lymphocytes with intrinsic tissue cells, such as MC, which may be relevant for organ specific, chronic inflammatory disorders.

Studies of the cellular infiltrate of chronic idiopathic urticaria: Prominence of T-lymphocytes, monocytes, and mast cells

We have used a panel of monoclonal antibodies and enzyme histochemistry in order to characterize further the perivascular mononuclear cell infiltrate found in chronic idiopathic urticaria. Biotinylated anti-mouse immunoglobulin was exposed to avidin-biotin-peroxidase-labeled complex followed by peroxidase development in order to detect binding of monoclonal antibodies. The mean percent staining obtained for 12 patients with chronic urticaria was 47% T-lymphocytes, 22% monocytes (14% by α-naphthyl acid esterase), and 11% mast cells. B-lymphocytes were not detectable, and approximately 20% of cells could not be identified. Although patients varied greatly in the ratio of Leu 3a positive helper-inducer T cells to T8 positive cytotoxic-suppressor cells, the average of all patients was not significantly different from the T4 T8 ratio in plasma. Our results suggest that the infiltrate resembles that observed in cellular immune reactions (although no antigen has been identified) and that interaction of T-lymphocytes and/or monocytes with mast cells to cause mediator release appears likely.

Interactions between macrophages and T-lymphocytes: Tumor sneaking through intrinsic to helper T cell dynamics

In a mathematical model of the cellular immune response we investigate immune reactions to tumors that are introduced in various doses. The model represents macrophage T-lymphocyte interactions that generate cytotoxic macrophages and cytotoxic T-lymphocytes. In this model antigens (tumors) can induce infinitely large T-lymphocyte effector populations because effector T-lymphocytes are capable of repeated proliferation and we have omitted immunosuppression. In this (proliferative) model small doses of weakly antigenic tumors grow infinitely large (i.e. sneak through) eliciting an immune response of limited magnitude. Intermediate doses of the same tumor induce larger immune responses and are hence rejected. Large doses of the tumor break through, but their progressive growth is accompanied by a strong immune response involving extensive lymphocyte proliferation. Similarly a more antigenic tumor is rejected in intermediate doses and breaks through in large doses. Initially small doses however lead to tumor dormancy. Thus although the model is devoid of explicit regulatory mechanisms that limit the magnitude of its response (immunosuppression is such a mechanism), the immune response to large increasing tumors may either be a stable reaction of limited magnitude (experimentally known as tolerance or unresponsiveness) or a strong and ever increasing reaction. Unresponsiveness can evolve because in this model net T-lymphocyte proliferation requires the presence of a minimum number of helper T cells (i.e. a proliferation threshold). Unresponsiveness is caused by depletion of helper T cell precursors.

Interaction of T-lymphocytes with the epidermis: immunopathological studies.

Journal of Cutaneous PathologyVolume 10, Issue 6 p. 540-549 Interaction of T-lymphocytes with the epidermis: immunopathological studies J. A. K. Patterson, Corresponding Author J. A. K. Patterson Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York, USAAddress: Jennifer A. K. Patterson, M. D., Department of Dermatology, Columbia-Presbyterian Medical Center. 630 West 168 Street, New York. NY 10032, USA.Search for more papers by this authorR. L. Edelson, R. L. Edelson Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York, USASearch for more papers by this author J. A. K. Patterson, Corresponding Author J. A. K. Patterson Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York, USAAddress: Jennifer A. K. Patterson, M. D., Department of Dermatology, Columbia-Presbyterian Medical Center. 630 West 168 Street, New York. NY 10032, USA.Search for more papers by this authorR. L. Edelson, R. L. Edelson Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York, USASearch for more papers by this author First published: December 1983 https://doi.org/10.1111/j.1600-0560.1983.tb01505.xCitations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume10, Issue6December 1983Pages 540-549 RelatedInformation

SB-restricted presentation of influenza and herpes simplex virus antigens to human T-Iymphocyte clones

The HLA-D region of the human major histocompatibility complex (MHC) has been shown to be homologous to the murine I region in terms of both structure and function. Both regions encode class II MHC molecules which restrict T-lymphocyte interactions with antigen-presenting cells. We have recently described the MHC restriction and antigen specificities of human T-lymphocyte clones directed at strain A influenza virus. The majority of T-lymphocyte clones recognized antigen in the context of cell surface interaction products encoded by HLA-D/DR genes. However, a few clones recognized antigen presented by cells histoincompatible for D/DR antigens. We report here that some of these clones recognized viral antigens in association with antigens encoded by genes identical with or closely linked to the recently described secondary B-cell (SB) locus of the MHC. This is the first report that SB-restricted antigen recognition may form an integral part of normal, human immune responses.

Macrophage--T-lymphocyte interaction in lichen planus. An electron microscopic and immunocytochemical study.

Papular lichen planus lesions from 12 patients were studied by a double-step immunocytochemical method to detect T-lymphocytes. Semithin sections were studied by light microscopy and ultrathin sections examined by electron microscopy. In the dermal infiltrate, many T-lymphocytes appeared closely juxtaposed to macrophages or Langerhans cells, frequently arranged in a rosette-like pattern. In the epidermis, T-lymphocytes were juxtaposed to macrophages or Langerhans cells and to degenerated keratinocytes. The close relationship between T-lymphocytes, macrophages or Langerhans cells and degenerated keratinocytes supports the hypothesis that lichen planus is immunological in nature: T-lymphocytes, after interacting with macrophages or Langerhans cells, become cytotoxic for keratinocytes.