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PubMed2005

Inhibitory control of TGF-beta1 on the activation of Rap1, CD11b, and transendothelial migration of leukocytes.

Beta2-integrins are a family of dimeric adhesion molecules expressed on leukocytes. Their capacity to bind ligand is regulated by their state of activation. CD11b, an alphaMbeta2 integrin, is implicated in a number of physiological and pathological events such as inflammation, thrombosis, or atherosclerosis. The GTPase Rap1 is essential for its activation and could therefore play a strategic role in the regulation of leukocyte functioning. Because low levels of circulating TGF-beta have been linked with severe atherosclerosis, we have assessed the role of this cytokine in the regulation of Rap1 and CD11b activation in differentiated U937 cells and in human peripheral blood monocytes. TGF-beta1 caused a significant reduction in the expression of CD11b but not in the expression of other integrins tested. More importantly, TGF-beta1 greatly reduced the capacity of PMA or chemokines to activate CD11b and Rap1, a phenomenon paralleled by a loss of the Epac transcript and a reduction in 8-pCPT-2'-O-Me-cAMP-mediated activation of Rap1. This inhibition diminished the capacity of monocytes to migrate across a monolayer of endothelial cells. The inhibitory effect of TGF-beta1 on Rap1 activity may exert a general protective influence against aberrant transendothelial migration, thereby holding inflammatory responses in check.

CD11b Antigen↗

PubMed1998

Function of porcine adhesion molecules in a human marrow microenvironment.

BACKGROUND: One way to circumvent the need for chronic immunosuppression in solid organ xenografting may be to induce donor-specific tolerance using bone marrow transplantation. If this approach is to succeed in the pig-to-human species combination, pig marrow must be capable of maturing into relevant tolerance-inducing cells and replenishing itself in host human marrow. One possible barrier is adhesion molecule incompatibility. We have studied the compatibility across the pig-human species barrier of two well-characterized ligands known to be important in hematopoiesis, CD44 and very late antigen (VLA)-4. METHODS: In vitro long-term bone marrow cultures were studied in which the effects of blocking antibodies were assessed by measuring cell numbers and colony-forming units. RESULTS: The blocking of CD44 had a comparable inhibitory effect on the hematopoiesis of human and pig marrow, even if the latter was maintained on a human stromal layer. Both cellular proliferation and colony-forming activity were inhibited by anti-CD44 monoclonal antibody. By contrast, a significant difference was observed in VLA-4 usage by hematopoietic cells of the two species. Blocking VLA-4 markedly inhibited human hematopoietic cellular proliferation but had no effect on pig hematopoiesis, on either porcine or human stroma. CONCLUSIONS: The data suggest that the incompatibility of either CD44 or VLA-4 is unlikely to limit the efficiency of porcine hematopoiesis in a human marrow environment. However, the difference in VLA-4 utilization between these species raises the possibility that other interactions may be important for effective porcine hematopoiesis and that their failure to function between species may contribute to the poor function of porcine hematopoietic cells in primate marrow microenvironments.

Animals↗

PubMed2005

Multiple sclerosis--novel insights and new therapeutic strategies.

PURPOSE OF REVIEW: This review focuses on novel aspects of the pathogenesis and advances in the therapy of multiple sclerosis (MS). RECENT FINDINGS: Recent observations suggest that early lesion development in MS may start in some forms with oligodendrocyte death and that inflammation appears as a secondary phenomenon only. The lack of sufficient remyelination in MS may be the result of a disturbed function of basic helix-loop-helix transcription factors. Clinically the identification of patients with a clinically isolated syndrome at high risk to develop clinically definite MS remains difficult; the predictive value of serum antibodies against myelin proteins remains controversial. The role of neutralizing antibodies in interferon therapy is discussed. New therapeutic approaches in MS are emerging. SUMMARY: The existing view on the pathogenesis of MS is still changing. The original assumption that cell-mediated demyelination is the key event in lesion development dictating clinical disability is critically reviewed and alternative pathways have been suggested. Oligodendrocyte death, axonal loss, the role of CD8 T lymphocytes, T regulatory cells, and B lymphocytes have come into the focus of newly evolving concepts in MS pathogenesis. A deepened understanding of the immunopathogenesis of this disease translates into innovative therapeutic approaches, such as blockade of alpha4 integrins by a humanized monoclonal antibody. In various animal models cell-replacement strategies yield promising results; however, turning these findings into an effective therapy in MS patients has a long way to go.

Animals↗

PubMed2006

Multiple sclerosis, natalizumab therapy, and progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: Multiple sclerosis affects many people, often in early adulthood, and causes significant disability. Natalizumab is a novel agent to be evaluated for multiple sclerosis and Crohn's disease that has demonstrated unique efficacy but has unfortunately been implicated in three cases of progressive multifocal leukoencephalopathy. This review covers the mechanism of action of natalizumab and efficacy for multiple sclerosis, the three cases of natalizumab-associated progressive multifocal leukoencephalopathy, our understanding of progressive multifocal leukoencephalopathy, and the mechanisms that may account for these events. RECENT FINDINGS: Natalizumab, an anti-alpha4-integrin antibody, binds to T-cell surface receptors to prevent migration from the circulation into the brain tissue. Phase II and III trials have been completed and demonstrate previously unseen efficacy in preventing relapses and disease progression. The cases of progressive multifocal leukoencephalopathy, two fatal and one disabling, resulted in the voluntary suspension of natalizumab and bring this entire class of agents into doubt. It is important to determine what led to the development of progressive multifocal leukoencephalopathy in the natalizumab-associated cases and to advance understanding and continue to develop therapies for the treatment of multiple sclerosis. SUMMARY: With ongoing safety evaluations, natalizumab is being reevaluated by the US Food and Drug Administration for possible reapproval and return to the market. If natalizumab is reapproved, challenging questions and issues will remain in treating patients with multiple sclerosis.

Adult↗

PubMed1995

Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation.

Vascular cell adhesion molecule-1 (VCAM-1) is expressed on vascular endothelium in a variety of inflammatory conditions and mediates leukocyte recruitment from blood into tissues. In this study we report a novel role for VCAM-1 in the formation of the umbilical cord and placenta during development. The murine VCAM1 gene was disrupted by targeted homologous recombination, and a distinct phenotype was found in VCAM-1-deficient embryos. At 8.5 days of gestation, the allantois failed to fuse to the chorion, resulting in abnormal placental development and embryonic death within 1-3 days. In addition, a role for VCAM-1 in early placental formation after chorioallantoic fusion was observed. In a minority of VCAM-1-deficient embryos, the allantois was able to fuse with the chorion, but the allantoic mesoderm was abnormally distributed over the chorionic surface. A small number of VCAM-1-deficient embryos survived, presumably by circumventing the placentation defects. They became viable and fertile adult mice with lack of VCAM-1 expression, normal organs, and an elevated number of circulating blood mononuclear leukocytes.

Allantois↗

PubMed2001

Purification, crystallization and preliminary X-ray diffraction studies of disintegrin (schistatin) from saw-scaled viper (Echis carinatus).

This is the first report of crystallographic data on a disintegrin molecule from any source. The heterodimeric disintegrin with a molecular weight of 14 kDa from Echis carinatus venom is a potent antagonist of alpha4 integrins. The intact disintegrin, containing two subunits A and B, was isolated and purified using affinity and ion-exchange columns. It has been crystallized using 1.6 M ammonium sulfate as a precipitating agent. The crystals grew to dimensions of 0.25 x 0.20 x 0.20 mm and diffracted to 2.5 A resolution. The crystals belong to space group I4(1)22, with unit-cell parameters a = b = 91.7, c = 55.1 A. Assuming a molecular weight of 14 kDa, a V(M) of 2.1 A(3) Da(-1) is obtained for one molecule of disintegrin in the asymmetric unit.

Animals↗

PubMed2005

A novel model of allograft rejection: immune reconstitution of Rag-1 recipients with 2C transgenic T-cell receptor lymphocytes.

The complexity of allorejection (cell activation, homing, and effector function) makes detailed studies difficult. We have developed a model of allograft rejection using purified monoclonal alloreactive effector cells. Immunodeficient C57Bl/6-Rag-1 (H-2(b)) recipients of Balb/c (H-2(d)) islet or skin grafts were reconstituted via adoptive transfer of splenocytes from 2C transgenic mice containing CD8+ cytotoxic effector cells directed against L(d). Recipients were assessed for engraftment, activation and homing of effector cells, and ability to reject grafts. Both unpurified 2C splenocytes and purified 2C/CD8+ cells durably reconstitute immunodeficient mice. Naive 2C effector cells reject skin grafts, but not islet allografts. However, when effector cells are primed prior to reconstitution, islet allografts are rejected. Using this model, blockade of adhesion molecules LFA-1 and alpha4-integrin delayed infiltration of islet allografts and prolonged allograft survival. This model of allorejection may be useful to study the activation and homing of allospecific cells in vivo.

Animals↗

PubMed2005

Analysis of the contributions of L-selectin and CXCR3 in mediating leukocyte homing to pregnant mouse uterus.

PROBLEM: Dynamic changes occur in endometrial immune cell populations during pregnancy but regulatory events promoting cell recruitment to the uterus are not established. Ovarian steroid hormones promote l-selectin and alpha4-integrin-mediated interactions between human peripheral natural killer (NK) cells and uterine endothelium while CXCR3, CXCR4 and their ligands are implicated in homing of human uNK cells to decidua. METHOD OF STUDY: Mice genetically-ablated for l-selectin or CXCR3 were studied. Morphometric analyses of implantation sites and assays of cell function (in vitro adhesion; in vivo homing following adoptive cell transfer) were undertaken. RESULTS: Leukocytes home to anti-mesometrial decidua with l-selectin making an early (<6 hr in vivo) contribution. Unexpectedly, CXCR3 deletion had no effect on homing but reduced the ability of uNK cells to modify placental spiral arterioles. CONCLUSIONS: Redundant mechanisms underlie homing of leukocytes to the uterus and their importance can be evaluated by an in vivo approach described herein.

Adoptive Transfer↗

PubMed2005

A review of trafficking and activation of uterine natural killer cells.

PROBLEM: Enrichment of uterine natural killer (uNK) cells occurs during pregnancy in many species. However, functions of uNK cells and regulation of their uterine homing are not fully defined. In mice and women, uNK cells contribute to angiogenesis, a role reviewed here and now addressed in a mammal with an alternative placental type. METHODS OF STUDY: To address lymphocyte functions, RNA from murine or porcine endometrium and lymphocytes purified from endometrium were analyzed using real-time or reverse transcription PCR. To address homing potential, human blood CD56(+) lymphocytes were evaluated using both RNA and functional adhesion to endothelium presented under shear force in frozen sections of gestation day 7 C57Bl/6J implantation sites. Women were serially sampled over a menstrual cycle or a clinical preparatory cycle for embryo transfer. RESULTS: Activation of murine uNK cells is associated with much greater increases in transcription for Eomes than for T-bet (Tbx21). Lymphocytes from normal porcine implantation sites transcribe vascular endothelial growth factor, placental growth factor, interferon-gamma and hypoxia-inducible factor (HIF)-1alpha. In fertile women, increases in L-selectin- and alpha4-integrin-mediated interactions between CD56(+) cells and endothelium occur at luteinizing hormone (LH) surge (cycling women) to oocyte pick up or embryo transfer, then return to pre-LH levels. CONCLUSIONS: Uterine lymphocytes may universally promote pregnancy-associated endometrial angiogenesis. Recruitment of uNK precursor cells from blood appears to occur in a window promoted by rising plasma estrogen and LH and limited by rising progesterone.

Animals↗

PubMed1998

Timing of effective natural killer cell collection in cancer patients after high dose chemotherapy, compared to peripheral blood stem cell collection.

Natural killer (NK) and lymphokine-activated killer (LAK) activities in patients with seminoma were determined, and the timing of effective NK cell collection was evaluated, compared to autologous peripheral blood stem cell (PBSC) collection. After chemotherapy, patients were injected with granulocyte-colony stimulating factor (G-CSF). CD56 cells decreased in parallel with white blood cells and then were restored. After discontinuing the G-CSF, the CD56 cells increased and reached peak 3-5 days after PBSC collection. The peak showed higher levels than those at premedication. Recovery-peripheral blood lymphocytes (PBL) which were obtained 4 days after PBSC collection showed higher NK and LAK activities than the PBL obtained before chemotherapy (Before-PBL). They exhibited a high expression of CD2, CD18, CD29, and CD49d. Furthermore, the LAK cells generated from the Recovery-PBL could acquire 9.6 folds of killer unit compared with the Before-PBL-LAK. These results suggest that, in order to obtain large numbers of NK cells, Recovery-PBL collection may be more advantageous than PBL collection in no relation with the chemotherapy.

Antigens, CD↗

PubMed1998

Molecular cloning and developmental expression of the Xenopus homolog of integrin alpha 4.

Integrin receptors containing an alpha 4 subunit mediate cell-cell adhesion by binding to VCAM and MadCAM-1 in addition to supporting cell-extracellular matrix (ECM) adhesion by binding to the alternatively spliced V-region of fibronectin (FN). Studies in chick and mouse embryos have implicated these integrins in neural crest migration, myotube formation, heart development, and placentation. Because integrin-FN adhesive interactions have been shown to play essential roles in mammalian development, studies were initiated of integrin alpha 4 in amphibian embryos, which are better suited to experimental analyses of the earliest stages of embryogenesis. Here, the cDNA cloning and pattern of expression of the Xenopus laevis homolog of integrin alpha 4 is reported. Xenopus alpha 4 is 55% identical at the amino-acid level to both its human and mouse counterparts, including conservation of an alpha 4-specific protease cleavage site, 11 potential N-linked glycosylation sites, and 24 cysteine residues. In situ hybridization analysis reveals that transcripts encoding alpha 4 are expressed in epidermis and the branchial arches. Although alpha 4 transcripts can be detected as early as gastrulation, the protein is observed only after tailbud stages of development and is spatially restricted to the epidermis and gills of tadpole stage embryos. From these data it is concluded that Xenopus integrin alpha 4 has structural features in common with other vertebrate alpha 4 homologs, but is detected in a more restricted tissue distribution during development than alpha 4 in other species.

Amino Acid Sequence↗

PubMed2003

Chorioallantoic morphogenesis and formation of the placental villous tree.

The placenta is a highly specialized organ whose primary function is to promote the exchange of nutrients and oxygen between maternal and fetal blood, essential for survival and growth of the baby. The surface area for nutrient transport is a highly convoluted villous structure that forms by branching morphogenesis. In mice, this process begins after embryonic day 8.5, following attachment of allantoic mesoderm to the chorion, and continues through the end of gestation. Gene targeting studies in mice have identified a large number of genes that are essential for chorioallantoic development to give rise to the layer of the placenta called the labyrinth. Collectively, these studies reveal that a number of signaling pathways regulate four distinct phases of labyrinth development: chorioallantoic attachment (involving VCAM1 and its receptor alpha4 integrin, Bmp5/7, and Wnt7b, as well as the cochaperone Mrj), initiation of branching (involving the Gcm1 transcription factor to select sites of branch initiation), extension of villous branching (involving FGF, EGF, and HGF/Met signaling, through the Grb2/Sos1/Mek1/p38alpha MAPK pathway), followed by vascularization of the villous tree. The restricted expression and/or action of the signaling components indicate that a series of intercellular interactions regulate chorioallantoic development.

Allantois↗

PubMed2000

Leukocyte recruitment and the acute inflammatory response.

Leukocyte recruitment is a hallmark feature of the inflammatory response. This review summarizes the generally accepted paradigm of leukocyte recruitment based on studies using intravital microscopy to visualize the microcirculation. The role of selectins and alpha4-integrin in rolling as well as integrin-mediated adhesion is discussed. However, it is becoming increasingly clear that the recruitment cascade within organs differs and therefore the review also attempts to highlight what is and is not known regarding leukocyte recruitment into the brain microvasculature. In the second part of this review, we provide some discussion of mechanisms by which the inflammatory response may be terminated. Particular emphasis on nuclear factor Nf kappaB and how IL10, IL13 and secreted leukocyte protease inhibitor (SLPI) may impact upon the Nf kappaB-dependent inflammatory response is presented.

Animals↗

PubMed2003

A small molecule alpha4beta1/alpha4beta7 antagonist differentiates between the low-affinity states of alpha4beta1 and alpha4beta7: characterization of divalent cation dependence.

An alpha4beta1/alpha4beta7 dual antagonist, 35S-compound 1, was used as a model ligand to study the effect of divalent cations on the activation state and ligand binding properties of alpha4 integrins. In the presence of 1 mM each Ca2+/Mg2+, 35S-compound 1 bound to several cell lines expressing both alpha4beta1 and alpha4beta7, but 2S-[(1-benzenesulfonyl-pyrrolidine-2S-carbonyl)-amino]-4-[4-methyl-2S-(methyl-[2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl]-amino) pentanoylamino]-butyric acid (BIO7662), a specific alpha4beta1 antagonist, completely inhibited 35S-compound 1 binding, suggesting that alpha4beta1 was responsible for the observed binding. 35S-Compound 1 bound RPMI-8866 cells expressing predominantly alpha4beta7 with a KD of 1.9 nM in the presence of 1 mM Mn2+, and binding was inhibited only 29% by BIO7662, suggesting that the probe is a potent antagonist of activated alpha4beta7. With Ca2+/Mg2+, 35S-compound 1 bound Jurkat cells expressing primarily alpha4beta1 with a KD of 18 nM. In contrast, the binding of 35S-compound 1 to Mn2+-activated Jurkat cells occurred slowly, reaching equilibrium by 60 min, and failed to dissociate within another 60 min. The ability of four alpha4beta1/alpha4beta7 antagonists to block binding of activated alpha4beta1 or alpha4beta7 to vascular cell adhesion molecule-1 or mucosal addressin cell adhesion molecule-1, respectively, or to 35S-compound 1 was measured, and a similar rank order of potency was observed for native ligand and probe. Inhibition of 35S-compound 1 binding to alpha4beta1 in Ca2+/Mg2+ was used to identify nonselective antagonists among these four. These studies demonstrate that alpha4beta1 and alpha4beta7 have distinct binding properties for the same ligand, and binding parameters are dependent on the state of integrin activation in response to different divalent cations.

Binding Sites↗

PubMed2004

Selective inhibition of inflammatory gene expression in activated T lymphocytes: a mechanism of immune suppression by thiopurines.

Azathioprine and 6-mercaptopurine are antimetabolite thiopurine drugs that play important roles in the treatment of leukemia and in the management of conditions requiring immunosuppression, such as inflammatory bowel disease. The biochemical pharmacology of these drugs suggests that inhibition of purine nucleotide formation through the 6-thioguanine nucleotide metabolites is their key molecular mechanism. However, it is unclear how these metabolites suppress immunity. We hypothesized that azathioprine produces a selective inhibitory effect on activated but not quiescent T lymphocytes. We first established a model system of T lymphocyte culture with azathioprine that produced pharmacologically relevant concentrations of 6-thioguanine nucleotides. Using genome-wide expression profiling, we identified a group of azathioprine-regulated genes in quiescent and activated T lymphocytes. Several genes involved in immunity and inflammation were selectively down-regulated by azathioprine in stimulated but not quiescent cells. Quantitative reverse transcription-polymerase chain reaction for three of these genes, tumor necrosis factor-related apoptosis-inducing ligand, tumor necrosis factor receptor superfamily member 7, and alpha4-integrin, confirmed down-regulated expression of transcript levels. Tumor necrosis factor-related apoptosis-inducing ligand protein expression was further studied and found to be inhibited by azathioprine, 6-mercaptopurine, and 6-thioguanine, implying that the inhibitory effects of azathioprine on expression are mediated by 6-thioguanine nucleotides. These results therefore provide a previously unrecognized molecular mechanism for the immunosuppressive properties of thiopurine antimetabolite drugs.

Annexin A5↗

PubMed1996

In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue.

Influenza virus infection induces the local production of gamma interferon (IFN-gamma) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN-gamma by using monoclonal antibodies. Neutralization of IFN-gamma led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum but had little effect on other isotypes. Studies on cells isolated from the lung parenchyma itself revealed that at the height of the immune response the ability of these cells to produce cytokines after antigen or T-cell receptor/CD3 stimulation was not affected. Ex vivo cytolytic activity by lung parenchyma cells, which is induced by infection with this virus in normal mice, was also found to be undisturbed by this treatment, even though anti-IFN-gamma antibody activity was recovered from lung lavage samples and sera at all days studied. Surprisingly, in vivo neutralization of IFN-gamma led to a significant reduction in the magnitude of the cellular infiltrate in the lung tissue which followed infection, suggesting an involvement of IFN-gamma in the mechanisms that regulate increased leucocyte traffic in the inflamed lung parenchyma. This conclusion was supported by findings of differences between mock-treated and anti-IFN-gamma-treated mice in the number of CD8+ lung T cells expressing CD49d (alpha4-integrin) and CD62L at various times after influenza virus infection. This study therefore demonstrates that IFN-gamma affects the local cellular response in the respiratory tract as well as the systemic humoral response to influenza virus infection.

Animals↗

PubMed2002

Spatial heterogeneity of TNF-alpha-induced T cell migration to colonic mucosa is mediated by MAdCAM-1 and VCAM-1.

Relatively little is known about how recirculation of lymphocytes through the inflamed intestinal mucosa is regulated. The aim of this study was to investigate the dynamic process of T lymphocyte-endothelial cell adhesion in TNF-alpha-challenged murine colonic mucosa by intravital microscopy. T lymphocytes from spleen (SPL) and intestinal lamina propria (LPL) were fluorescence labeled, and their adhesion to microvessels in the colonic mucosa was observed. In TNF-alpha (25 microg/kg)-stimulated colonic venules, an enhanced adhesion of SPL and LPL was demonstrated, with dominant recruitment of LPLs. The magnitude of the increased LPL adhesion was more significant in the colon than in the small intestine. These T lymphocyte interactions in the colonic mucosa were significantly reduced by blocking MAbs against either mucosal addressin cell adhesion molecule-1 (MAdCAM-1), VCAM-1, alpha(4)-integrin, or beta(7)-integrin but not by anti-ICAM-1. Immunohistochemistry revealed significant MAdCAM-1 expression in the lamina propria and VCAM-1 expression in the submucosa of TNF-alpha-treated colon. Spatial heterogeneity of MAdCAM-1 and VCAM-1 activation following TNF-alpha challenge may promote specific T lymphocyte recruitment in the inflamed colonic mucosa.

Animals↗

PubMed2000

The effect of antigen stimulation on alpha(4), beta(1) and beta(7) chain integrin expression and function in CD4+ cells.

BACKGROUND: The alpha(4) integrin, as alpha(4)beta(1) (VLA-4) or alpha(4)beta(7), is critical for T cell migration and proliferation, although its functional modulation remains poorly understood. We hypothesized that increased receptor density, based on new receptor chain synthesis, was one such mechanism. We examined the surface receptor density of the alpha(4) and beta(1) chains on CD4+CD45RO+ cells, and the mRNA expression of these and the beta(7) chain in response to allergen and nonallergen antigen stimulation. METHODS: Flow-cytometric analyses for CD49d, CD29, and CD45RO were performed on T cell lines specific for timothy, tetanus, and Candida from atopic and nonatopic donors. RNA was extracted from cells sorted to select CD4+/CD49d-positive cells before and after stimulation. Equivalent amounts of cDNA for beta-actin, alpha(4), beta(1) and beta(7) were used in PCR, and the products were quantified using phosphoimaging. RESULTS: CD49d expression is heterogeneous on T cell lines and is upregulated by antigen stimulation on CD4+ T cells. The surface expression on CD4+CD45RO+ timothy allergen or tetanus toxoid T cell lines is at least double that found on CD45RO- cells. Antigen stimulation upregulated CD49d expression on the CD4+CD45RO+ subpopulation of both cell lines although it was not as significant as in the case of all CD4+ T cells. CD29 surface expression behaves similarly. Candida had no effect on CD49d or CD29. Messenger RNA expression for the alpha(4) chain (CD49d) is significantly upregulated 48 h following the addition of timothy or tetanus. beta(7) chain expression also rises significantly on both cell lines. beta(1) chain expression increases, but not significantly. CONCLUSIONS: The surface expression of the CD49d is heterogeneous and much higher on CD4+CD45RO+ cells than on CD4+RO- T cells. The CD49d integrin chain on CD4+ T cells is upregulated following antigen exposure. However, the CD4+CD45RO+ subpopulation is only partially responsible for this increase suggesting other T cells to have this receptor expression upregulated. CD29 expression behaves similarly. Messenger RNA expression increases coordinately for alpha(4), beta(7), and not significantly for beta(1) in these cells. These observations provide a potential mechanism for the selective accumulation of T cells at sites of inflammation, and suggest an important point of intervention for allergic and inflammatory disease.

Allergens↗