Biomedical subjects

Kouji Matsushima

Publications and source records attributed to Kouji Matsushima.

At least 19 recordsLinked to original sources

PubMed2007

Aberrant B1 cell trafficking in a murine model for lupus.

B lymphocyte chemoattractant (BLC/CXCL13) is ectopically and highly expressed in the target organs such as the thymus and kidney in aged (NZB x NZW)F1 (BWF1) mice, a murine model for SLE. Ectopic expression of BLC/CXCL13 was attributed to mature myeloid DCs infiltrating in the target organs. DCs were also increased in the peripheral blood in aged BWF1 mice and differentiated into BLC/CXCL13-producing DCs in the presence of TNF-alpha or IL-1beta, but not IFN-alpha or IFN-gamma. BLC/CXCL13 expression in mature myeloid DCs was confirmed in bone marrow derived-DCs generated in vitro in the presence of GM-CSF and TNF-alpha. B1 cells expressed higher level of CXCR5 and migrated towards BLC/CXCL13 much better than B2 cells. B1 cells failed to home to the peritoneal cavity and preferentially recruited to the target organs in aged BWF1 mice developing lupus nephritis. B1, but not B2 cells possessed a potent antigen presenting activity in allo-MLR and activated autologous thymic CD4 T cells in the presence of IL-2. CXCR5+ CD4 T cells were also increased in aged BWF1 mice and they enhanced IgG production by B1 cells in vitro. These results suggest a possible involvement of aberrant B1 cell trafficking in activation of autoreactive CD4 T cells and autoantibody production in the target organs during the development of lupus, providing a new insight for the pathogenesis of B1 cells in lupus.

Animals↗

PubMed2006

Maintenance of memory CD8+ T cell diversity and proliferative potential by a primary response upon re-challenge.

Memory CD8+ T cells generated during an immune response are long lived and self-renewing, offering enhanced host protection against re-infection. However, how an antigen-specific population of memory T cells is maintained, throughout repetitive infections over potentially a lifetime, is not known. Here we show that a primary response during re-challenge significantly contributes to memory T cell pool both qualitatively and quantitatively. Upon re-challenge, the skewed Vbeta usage and TCR repertoire of pre-existing memory T cells is partly corrected by diversity in a newly primed (primary) T cell population. Importantly, this primary population expands more vigorously in a subsequent antigen encounter. These findings indicate that memory T cell populations evolve over multiple challenges, favoring memory T cells generated in more recent encounters, and suggest that these primary populations have essential roles in the perpetuation of antigen-specific T cell populations.

Animals↗

PubMed2006

Synovial autoreactive T cells in rheumatoid arthritis resist IDO-mediated inhibition.

A hallmark of T cell-mediated autoimmunity is the persistence of autoreactive T cells. However, it remains to elucidate the manner in which synovial T cells are sustained in patients with rheumatoid arthritis (RA). We found that dendritic cells (DC) and tissues from the synovial joints of RA patients expressed higher levels of IDO than DC from healthy donors. Interestingly, T cells derived from the joint synovial fluid (SF) of RA patients proliferated in response to either autologous or allogeneic IDO-positive DC, an outcome that was not affected by the addition of IDO inhibitor 1-methyl-D-tryptophan (1-MT). In contrast, addition of 1-MT to the culture stimulated with allogeneic or autologous IDO-positive DC significantly enhanced the proliferation of T cells derived from peripheral blood of healthy donors or from peripheral blood of RA patients. Furthermore, we found that functionally active tryptophanyl-tRNA-synthetase (TTS) was significantly elevated in T cells derived from the SF of RA patients, leading to enhanced storage of tryptophan in T cells and to subsequent resistance to IDO-mediated deprivation of tryptophan. The RA SF enhancement of TTS expression in T cells was blocked by mAb to IFN-gamma and TNF-alpha. These results suggest that the resistance of T cells to IDO-mediated deprivation of tryptophan represents a mechanism by which autoreactive T cells are sustained in vivo in RA patients. Specifically, blocking of the up-regulation of TTS expression in T cells presents an avenue for development of a novel therapeutic approach to treatment of RA.

Adult↗

PubMed2006

Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation.

Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.

Cell Line↗

PubMed2006

Intervention of MAdCAM-1 or fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects.

Coincidence of the beneficial graft-vs.-tumor (GVT) effects and the detrimental graft-vs.-host disease (GVHD) remains the major obstacle against the widespread use of allogeneic bone marrow transplantation (BMT) as tumor immunotherapy. We here demonstrate that intervention of MAdCAM-1 (mucosal vascular addressin cell adhesion molecule-1) or fractalkine/CX3CL1 after the expansion of allo-reactive donor CD8 T cells selectively inhibits the recruitment of effector donor CD8 T cells to the intestine and alleviates the graft-vs.-host reaction (GVHR) associated intestinal injury without impairing GVT effects. In a nonirradiated acute GVHD model, donor CD8 T cells up-regulate the expression of intestinal homing receptor alpha4beta7 and chemokine receptors CXCR6 and CX3CR1, as they differentiate into effector cells and subsequently infiltrate into the intestine. Administration of anti-MAdCAM-1 antibody or anti-fractalkine antibody, even after the expansion of alloreactive donor CD8 T cells, selectively reduced the intestine-infiltrating donor CD8 T cells and the intestinal crypt cell apoptosis without affecting the induction of donor derived anti-host CTL or the infiltration of donor CD8 T cells in the hepatic tumor. Moreover, in a clinically relevant GVHD model with myeloablative conditioning, these antibodies significantly improved the survival and loss of weight without impairing the beneficial GVT effects. Thus, interruption of alpha4beta7-MAdCAM-1 or CX3CR1-fractalkine interactions in the late phase of GVHD would be a novel therapeutic approach for the separation of GVT effects from GVHR-associated intestinal injury.

Animals↗

PubMed2006

Trans-basement membrane migration of human basophils: role of matrix metalloproteinase-9.

In allergic disorders, basophils migrate from the blood stream to inflamed tissue sites. Since trans-basement membrane migration is an important step for local basophil accumulation, we performed a human basophil transmigration assay using a model basement membrane, Matrigel. IL-3 in the upper chamber was critical for basophil trans-basement membrane migration over baseline levels, since none of the chemoattractants placed in the lower chambers induced migration. RANTES, IL-8, 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) and platelet-activating factor (PAF) significantly up-regulated the transmigration of IL-3-treated basophils. Neutralizing experiments indicated the involvement of beta2 integrin and matrix metalloproteinase (MMP)-2/9 in basophil transmigration. Real-time quantitative PCR revealed that basophils constitutively expressed transcripts for MMP-9, and at lower levels, MMP-2, but cell-surface expression was only detected for MMP-9. MMP-9 was also detected in the cytoplasm and culture supernatant of the basophils. Treatment with IL-3 up-regulated the surface level of MMP-9 on the basophils. Our results suggest that basophils possess a unique regulatory mechanism for trans-basement membrane migration which is affected by cytokines, chemoattractants, beta2 integrin and MMPs, especially MMP-9. MMP-9 may be critically involved in the pathogenesis of local basophil influx in allergic diseases.

Basement Membrane↗

PubMed2006

SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus.

A vaccine for severe acute respiratory syndrome (SARS) is being intensively pursued against its re-emergence. We generated a SARS coronavirus (SARS-CoV) spike protein-expressing recombinant vaccinia virus (RVV-S) using highly attenuated strain LC16m8. Intradermal administration of RVV-S into rabbits induced neutralizing (NT) antibodies against SARS-CoV 1 week after administration and the NT titer reached 1:1000 after boost immunization with RVV-S. Significantly, NT antibodies against SARS-CoV were induced by administration of RVV-S to rabbits that had been pre-immunized with LC16m8. RVV-S can induce NT antibodies against SARS-CoV despite the presence of NT antibodies against VV. These results suggest that RVV-S may be a powerful SARS vaccine, including in patients previously immunized with the smallpox vaccine.

Animals↗

PubMed2006

Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis.

Fibrocytes are a distinct population of bloodborne cells that share markers of leukocytes as well as mesenchymal cells. We hypothesized that CCR7-positive fibrocytes migrate into the kidney in response to secondary lymphoid tissue chemokine (SLC/CCL21) and contribute to renal fibrosis. To investigate this hypothesis, renal fibrosis was induced by unilateral ureteral obstruction in mice. A considerable number of fibrocytes dual-positive for CD45 and type I collagen (ColI) or CD34 and ColI infiltrated the interstitium, reaching a peak on day 7. Most fibrocytes were positive for CCR7, and CCL21/CCR7 blockade reduced the number of infiltrating fibrocytes. CCL21 and MECA79 dual-positive vessels were also detected in the interstitium. The blockade of CCL21/CCR7 signaling by anti-CCL21 antibodies reduced renal fibrosis, which was confirmed by a decrease in fibrosis in CCR7-null mice with concomitant reduction in renal transcripts of pro alpha1 chain of ColI and TGF-beta1. The number of F4/80-positive macrophages decreased along with renal transcripts of monocyte chemoattractant protein 1 (MCP-1/CCL2) after the blockade of CCL21/CCR7 signaling. These findings suggest that CCR7-positive fibrocytes infiltrate the kidney via CCL21-positive vessels, thereby contributing to the pathogenesis of renal fibrosis. Thus, the CCL21/CCR7 signaling of fibrocytes may provide therapeutic targets for combating renal fibrosis.

Animals↗

PubMed2006

Reduction in chronic allograft nephropathy by inhibition of p38 mitogen-activated protein kinase.

BACKGROUND: Chronic allograft nephropathy (CAN) is the major cause for late graft loss and is therefore a key target for therapy. METHODS: The impact of p38 mitogen-activated kinase (MAPK) on CAN was investigated by administering FR167653 (32 mg/kg/day), a specific inhibitor of p38 MAPK, for 4 weeks in addition to conventional cyclosporine therapy (1.5 mg/kg/day for 5 days) in an established experimental rat transplantation model. RESULTS: Transplanted rats develop glomerulosclerosis, arterial obliteration, interstitial fibrosis and tubular atrophy, all of which are characteristic of CAN, resulting in shortened survival on 32 weeks. However, the inhibition of p38 MAPK by daily subcutaneous treatment with FR167653 resulted in reduced CAN with preserved renal function and prolonged survival. The FR167653-treated rats had fewer phosphorylated p38 MAPK-positive cells in treated kidneys. Concomitantly, the expression of monocyte chemoattractant protein-1/CCL2 and transforming growth factor-beta(1) was markedly reduced. CONCLUSION: These results suggest that p38 MAPK phosphorylation is involved in the pathogenesis of CAN and provide evidence that p38 MAPK is a novel, appealing therapeutic target for combating CAN.

Animals↗

PubMed2006

Expression and function of toll-like receptors in human basophils.

We investigated the expression and function of a panel of Toll-like receptors (TLRs) in human basophils. Basophil preparations constitutively expressed TLR2, TLR4, TLR9 and TLR10 mRNAs (TLR4 > TLR2 >> TLR9, TLR10). Although TLR mRNA expression in basophils was generally less prominent compared with those in neutrophils and monocytes, basophils expressed significantly higher levels of TLR2 and TLR4 mRNA than eosinophils. Various TLR ligands (Pam3Cys-Ser-Lys4, poly I:C, lipopolysaccharide, R-848, CpG DNA) were tested, but none affected the expression level of adhesion molecule CD11b or the viability of freshly purified basophils. On the other hand, when basophils were pretreated with interferon-gamma before stimulation with TLR ligands, only the TLR4 ligand, lipopolysaccharide, upregulated CD11b expression. However, the surface levels of TLR2 and TLR4 on the interferon-gamma-treated basophils showed no obvious changes. These results suggest that TLR4 on basophils may be involved in the pathogenesis of infection-induced exacerbation of allergic inflammation by modulating basophil functions.

Basophils↗

PubMed2006

Dynamics of dendritic cell migration and the subsequent induction of protective immunity in the lung after repeated airway challenges by nontypeable Haemophilus influenzae outer membrane protein.

To determine the dynamics of dendritic cell (DCs) migration and their role in recurrent infections by nontypeable Haemophilus influenzae (NTHi), the migration of mature DC into pulmonary lymph nodes (LN) and the development of a P6-specific immune response and bacterial clearance in the lung were examined after repeated airway challenges with outer membrane protein (OMP) at 1-week intervals in mice. Although the migration of mature DC into the pulmonary LN is attenuated after repeated airway challenge with OMP, the in vitro P6-specific T cell proliferation in the cultured pulmonary LN cells was enhanced and was subsequently linked to the development of P6-specific IgA production and the development of protective immunity in the airway of mice.

Administration, Inhalation↗

PubMed2006

Production of two novel monoclonal antibodies that distinguish mouse lymphatic and blood vascular endothelial cells.

We produced two novel rat monoclonal antibodies (LA102 and LA5) to identify mouse lymphatic vessels and blood vessels, respectively. We characterized the two antibodies as to the morphological and functional specificities of endothelial cells of both types of vessels. The antibodies were produced by a rapid differential immunization of DA rats with collagenase- and neuraminidase-treated mouse lymphangioma tissues. LA102 specifically reacted with mouse lymphatic vessels except the thoracic duct and the marginal sinus of lymph nodes, but not with any blood vessels. In contrast, LA5 reacted with most mouse blood vessels with a few exceptions, but not with lymphatics. LA102 recognized a protein of 25-27 kDa, whereas LA5 recognized a molecule of 12-13 kDa. Neither antibody recognized any currently identified lymphatic or vascular endothelial cell antigens. Immunoelectron microscopy revealed that the antigens recognized by LA102 and LA5 were localized on both luminal and abluminal endothelial cell membranes of each vessel type. Interestingly, LA102 immunoreactivity was strongly expressed on pinocytic or transport vesicle membrane in the cytoplasm of lymphatic endothelium. Besides endothelial cells, both antibodies also recognized some types of lymphoid cells. Since, the LA102 antigen molecule is expressed on some lymphoid cells, it may play important roles in the migration of lymphoid cells and in some transport mechanisms through lymphatic endothelial cells.

Animals↗

PubMed2006

Absence of IL-1 receptor antagonist impaired wound healing along with aberrant NF-kappaB activation and a reciprocal suppression of TGF-beta signal pathway.

Although enhanced expression of IL-1 family proteins, including IL-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) during wound healing has been observed, the pathophysiological roles of these factors, particularly IL-1ra, still remain elusive. We explored skin wound-healing processes in IL-1ra-deficient mice. Compared to wild-type (WT) mice, IL-1ra-deficient mice exhibited impaired wound healing, as evidenced by attenuated collagen deposition and delayed neovascularization. In contrast, neutrophil recruitment was significantly exaggerated, with the augmented expression of IL-1s, TNF-alpha, and CXC chemokines, MIP-2 and KC, in IL-1ra-deficient mice compared with WT mice. Because the transcription of these proinflammatory cytokines and CXC chemokines requires the activation of NF-kappaB, a major target of IL-1- and TNF-alpha-mediated signal pathway, we examined the activation states of NF-kappaB. Nuclear translocation of NF-kappaB p65 was significantly enhanced and prolonged in IL-1ra-deficient mice, compared to that in WT mice. The cross-talk between NF-kappaB and TGF-beta-mediated signals has been proposed based on in vitro observations. Indeed, compared to WT mice, the amounts of total and phosphorylated Smad2 and Smad3 were decreased with a reciprocal increase in the amount of Smad7 in skin wound sites of IL-1ra-deficient mice. Moreover, the gene expression of vascular endothelial growth factor, a target gene of TGF-beta1, was decreased in IL-1ra-deficient mice. Thus, the absence of IL-1ra may suppress TGF-beta-mediated signaling pathway, which is crucial for collagen deposition and vascular endothelial growth factor-mediated neovascularization in wound healing.

Animals↗

PubMed2006

MCP-1/CCR2-dependent loop for fibrogenesis in human peripheral CD14-positive monocytes.

Monocyte/macrophage (Momicron) migration to sites of inflammation is a prerequisite cause of organ fibrosis. The recruitment and activation of Mo are regulated by C-C chemokines, especially monocyte chemoattractant protein-1 [(MCP-1)/CC chemokine ligand 2], which interacts with CC chemokine receptor 2 (CCR2). However, the mechanisms leading to fibrosis via MCP-1/CCR2 signaling in Mo remain to be investigated. The effect of MCP-1 on the expression of MCP-1, CCR2, transforming growth factor-beta1 (TGF-beta1), and type I collagen in circulating human CD14-positive Mo was investigated. In addition, the impact of MCP-1-specific or TGF-beta1-specific antisense (AS) phosphorothioate oligodeoxynucleotides (ODN) was examined to explore the involvement of autocrine/paracrine production of MCP-1 and TGF-beta1 by human CD14-positive Mo. Furthermore, specific CCR2 inhibitors were applied to examine the involvement of CCR2 signaling for the promotion of a fibrogenic response. The stimulation of Mo with MCP-1 increased mRNA levels of TGF-beta1 and a pro-alpha1 chain of type I collagen (COL1A1) as well as protein synthesis. Similarly, the expression of MCP-1 and CCR2 was enhanced by the stimulation with MCP-1 in dose- and time-dependent manners. This positive loop via MCP-1 was reduced by pretreatment with MCP-1-specific AS-ODN. It was also noted that pretreatment with TGF-beta1-specific AS-ODN partially reduced COL1A1 mRNA levels. Finally, transcripts of these molecules were suppressed by pretreatment with specific CCR2 inhibitors. The present study demonstrated that human peripheral CD14-positive Mo contribute directly to fibrogenesis by a MCP-1/CCR2-dependent amplification loop. These data suggest that fibrogenic processes in Mo regulated by MCP-1/CCR2 may be novel, therapeutic targets for combating organ fibrosis.

Cells, Cultured↗

PubMed2006

Regulatory T cells induce a privileged tolerant microenvironment at the fetal-maternal interface.

The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN-gamma and TNF-alpha were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-beta and heme oxygenase-1 at the fetal-maternal interface were dramatically up-regulated after Treg transfer, while the levels of indolamine 2,3-dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.

Adoptive Transfer↗

PubMed2006

Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia-reperfusion injury.

OBJECTIVE: Ischemia-reperfusion injury is known to cause organ failure, but the mechanisms of pathogenesis remain unclear. Inflammation is a factor in tissue destruction in ischemia reperfusion injury, and interleukin (IL)-1 is a key promoter of inflammation. DESIGN: Prospective, randomized, and controlled study. SETTING: University laboratory. SUBJECTS: Male mice 6-8 wks of age, in which genes for IL-1alpha and IL-1beta (IL-1alpha/beta deficient) and IL-1 receptor antagonist (IL-1RA deficient) are deleted by homologous recombination, and wild-type controls on a Balb/c background. INTERVENTIONS: In this study, the role of IL-1 on inflammatory cascades, including chemokine expression, inflammatory cell infiltration, and tissue destruction, was investigated in 45 mins of unilateral renal ischemic injury using IL-1alpha/beta-deficient mice and IL-1RA-deficient mice. In addition, the effects of IL-1 on chemokine expression in cultured tubular epithelial cells were investigated. MEASUREMENTS AND MAIN RESULTS: In vivo study revealed that the number of interstitial infiltrated neutrophils and macrophages, which accompanied the increase of the serum levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-1alpha, respectively, significantly increased in IL-1RA-deficient mice. The number of interstitial infiltrated neutrophils correlated well with serum levels of KC at 24 hrs after reperfusion, whereas the number of interstitial infiltrated macrophages correlated well with the serum levels of MIP-1alpha and monocyte chemoattractant protein (MCP)-1 at 24 and 48 hrs after reperfusion, respectively. Likewise, in vitro study revealed that stimulation of tubular epithelial cells by IL-1beta and/or H2O2 sequentially induced KC, MIP-1alpha, and MCP-1 in both protein and messenger RNA levels, which is consistent with in vivo results. CONCLUSION: IL-1-dependent inflammatory cascades, followed by inflammatory cell infiltration and subsequent tissue destruction, may affect pathogenesis of renal ischemia-reperfusion injury.

Animals↗

PubMed2006

Asthma severity is associated with an increase in both blood CXCR3+ and CCR4+ T cells.

OBJECTIVES: A predominance of type 2 helper T cells (Th2) in the bronchoalveolar space and peripheral blood is a well-accepted feature of bronchial asthma. However, the relationship between peripheral blood Th2 cells and asthma severity has not been thoroughly investigated. METHODS: As Th1 cells predominantly express the chemokine receptor CXCR3 and Th2 cells express CCR4, we assessed the distribution of peripheral blood CXCR3+ and CCR4+ lymphocytes using flow cytometry in 186 patients with asthma and 75 normal subjects. RESULTS: The proportion of CXCR3+/CD45RO+ cells in CD4+ T cells increased as the severity of asthma increased. The percentage of CCR4+/CD45RO+ cells in CD4+ T cells were elevated in mild to severe asthma patients compared with controls. However, there was no significant difference in CCR4+/CD45RO+ cells between the mild to severe asthma patients. There was no relationship between the patient's age and the numbers of CXCR3+ or CCR4+ T cells. The percentage of CCR4+ cells in CD45RO+/CD4+ T cells correlated with the levels of total serum IgE (r = 0.630, P < 0.0001). CONCLUSIONS: The proportion of CCR4+ cells in blood memory helper T cells may be increased in patients with asthma and is associated with the level of serum IgE, but severity of asthma is also associated with the increase of blood CXCR3+ cells in memory helper T cells.

Adult↗

PubMed2005

Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis X, a selectin ligand expressed on a subset of skin-homing helper memory T cells.

We previously identified the carbohydrate determinant sialyl 6-sulfo Lewis X (Le(x)) as the major L-selectin ligand on high endothelial venules of peripheral lymph nodes. In this study, we examined the distribution of the sialyl 6-sulfo Le(x) determinant among peripheral lymphocytes. The determinant was expressed on a subset of helper memory T and NK cells. The helper memory T cells expressing sialyl 6-sulfo Le(x) were CD45RO(bright+) PSGL-1(high+) CCR4+ L-selectin+ CCR7+ but did not express alpha4beta7 integrin or CCR9, indicating that they were the skin-homing population of central memory T cells. The T-cell subset significantly expressed mRNA for 6-sulfotransferase HEC-GlcNAc6ST and fucosyltransferase Fuc-T VII, responsible for the synthesis of sialyl 6-sulfo Le(x). Characteristics of the T-cell population were similar to those previously described for cutaneous lymphocyte-associated antigen (CLA)-positive T cells defined by the HECA-452 or 2F3 antibody. The binding of the T-cell subset with the specific anti-sialyl 6-sulfo Le(x) antibody G152 was almost completely abrogated by HECA-452 or 2F3. Binding of recombinant E-, P-, and L-selectins to the T-cell subset was significantly inhibited by G152 and by HECA-452 antibodies. We propose that CLA, which is expressed without any activation stimuli on peripheral skin-homing helper memory T cells in healthy persons, is at least partly the sialyl 6-sulfo Le(x) determinant.

Antibodies, Monoclonal↗