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Biomedical subjects

A Scheynius

Publications and source records attributed to A Scheynius.

At least 55 records · Page 3Linked to original sources
PubMed1997

Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease.

The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor beta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-beta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 +/- 1 y (mean +/- SD), with a body mass index (BMI; in kg/m2) of 17.2 +/- 0.5 and various noncancer disorders, and 22 healthy matched control subjects aged 72 +/- 1 y, with a BMI of 25.4 +/- 0.7 (significantly different from patients, P < 0.001), were included. Fifteen patients and their corresponding control subjects were reexamined 3 mo later. Isolated monocytes were stimulated with lipopolysaccharide (LPS) and concentrations of IL-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrations of IL-6, IL-1ra, IL-10, TGF-beta 1, and acute-phase reactants were analyzed. Serum concentrations of orosomucoid and IL-6 were higher in the malnourished subjects than in the control subjects (1.14 +/- 0.1 compared with 0.8 +/- 0.3 g/L, P < 0.001; and 5 ng/L compared with undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1 beta (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was found in monocytes from patients with PEM relative to the control subjects when monocytes were stimulated with 0.1 microgram LPS/L. Monocyte TNF generation and serum concentrations of IL-10, IL-1ra, and TGF-beta 1 did not differ. Similar results were obtained at follow-up. IL-1ra was negatively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cytokines such as IL-6 and IL-1 beta in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.

Aged↗
PubMed1997

Is the sanctuary where Helicobacter pylori avoids antibacterial treatment intracellular?

The sanctuary site where Helicobacter pylori evades antimicrobial therapy is unknown, but considerable data exist about an intracellular location for H pylori. Ten H pylori-infected volunteers received standard triple antimicrobial therapy for 2 weeks. Gastric mucosal biopsy specimens were obtained with jumbo forceps on therapy days 0, 3, 14, and 42. Hematoxylin-eosin staining was used for classification of gastritis and the Genta stain for the visualization of H pylori. Immunohistochemical staining was used to detect HLA-DR antigens, human heat shock protein (HSP60), and the bacterial HSP60 antigen. Bacterial HSP60 was expressed on the mucosal surface and within epithelial cells. No such expression of human HSP60 was found, which supports a bacterial origin for the intracellular HSP60. Coexpression of bacterial HSP60 and HLA-DR was always observed, indicating an ongoing local immune response. Infection was cleared on day 14, but when examined 4 weeks after completion of therapy, Genta staining indicated that only five volunteers remained free of H pylori. However, results of immunohistochemical staining were negative at this time for only two volunteers. Disappearance of intracellular expression of bacterial HSP60 remained after therapy and correlated with the intensity of chronic inflammatory cell infiltration. These data are consistent with the intracellular localization of H pylori having a role in inflammation and as a protective strategy against extracellular antibacterial activity.

Adult↗
PubMed1997

Intracellular reservoir of Streptococcus pyogenes in vivo: a possible explanation for recurrent pharyngotonsillitis.

Numerous theories have been presented that attempt to explain the frequent recurrences of pharyngotonsillitis caused by Streptococcus pyogenes; these recurrences occur after seemingly adequate antibiotic treatment. We previously have demonstrated that Spyogenes can survive for up to 7 days intracellularly in immortalized human respiratory epithelial cells grown in an antibiotic supplemented medium. Viable S pyogenes were externalized and established an extracellular infection, whenever the extracellular antibiotic was removed. We have investigated the presence of intracellular S pyogenes in two in vivo studies using respiratory epithelial cells collected from patients with tonsillitis and the tonsils of asymptomatic carriers. Electron microscopy and immunohistochemistry demonstrated intracellular S pyogenes in pharyngeal epithelial cells in 13 of 14 patients with tonsillitis (93%). Furthermore, intracellular S pyogenes were found in macrophage-like cells in eight (73%) and in epithelial cells in four (36%) tonsils from 11 asymptomatic S pyogenes carriers. These in vivo data strongly support the hypothesis that intracellular S pyogenes can constitute a reservoir of bacteria with the potential to cause reinfections.

Adolescent↗
PubMed1997

Age governs gender-dependent islet cell autoreactivity and predicts the clinical course in childhood IDDM.

Most IDDM patients temporarily restore some of their beta-cell function following the initiation of insulin therapy. The aim of this study was to analyse the influence of age, gender, metabolic state at diagnosis and presence of autoantibodies (GAD65 antibodies and ICA) on the duration of the clinical partial remission. In total, 149 consecutively diagnosed IDDM children, 0-16 y old (70F, 79M, mean age 9.5 y) were studied. Partial remission was arbitrarily defined as the period when the insulin dose was below 0.5 U/BW 24 h-1 and HbA1c below 7.5%, and occurred in 119/149 patients with a duration between 1 and 38 months. Cox's regression analysis showed that the factors significantly associated with the duration of remission were age, gender, interaction between age and gender, ICA and a high initial HbA1c, whereas GAD65Ab had no influence. Young boys had the shortest remission period, while adolescent boys had the longest, as compared to young and adolescent girls. The ICA-negative patients (n = 42) had a longer remission period (median 9.7 months) than the ICA-positive children (n = 107; 5.0 months; p = 0.0001), regardless of GAD65Ab status. We speculate that the relative insulin resistance, which is more pronounced in pubertal girls than in boys, may be associated with a more rapid increase of exogenous insulin requirement. These findings are important when evaluating the effect of islet cell autoreactivity on the clinical course of IDDM in children.

Adolescent↗
PubMed1997

The skin and the gut in psoriasis: the number of mast cells and CD3+ lymphocytes is increased in non-involved skin and correlated to the number of intraepithelial lymphocytes and mast cells in the duodenum.

The aim of this work was to study tryptase+ mast cells and CD3+ T lymphocytes in non-involved skin in psoriasis and their possible relation to mast cells and lymphocytes in the duodenal mucosa. Skin biopsy specimens were obtained from 43 patients with psoriasis of variable severity and from 10 healthy subjects. Compared with the reference subjects, the number of mast cells in non-involved skin was clearly increased, most markedly in the papillary dermis. The increase was present both in mild, moderate and severe psoriasis. CD3+ lymphocytes were increased in non-involved skin in moderate and severe psoriasis. Patients with an increased number of duodenal intraepithelial lymphocytes had significantly more mast cells in non-involved skin than those without such an increase, and there was a significant correlation between the number of mast cells in non-involved skin and score for intraepithelial lymphocytes. However, when the 14 patients with increased intraepithelial duodenal lymphocytes were excluded-as they may represent a separate type of psoriasis-another type of correlation between the skin and the duodenal mucosa was found, namely a highly significant inverse correlation between the number of CD3+ lymphocytes in non-involved skin and the number of duodenal mast cells, which is highly elevated in psoriasis. The results might indicate an interplay between skin and intestinal mast cells and lymphocytes in a hitherto unknown way.

Adult↗
PubMed1997

Cell surface expression of two major yeast allergens in the Pityrosporum genus.

BACKGROUND: We have previously identified two major allergens of Pityrosporum orbiculare and characterized these as 37 kDa and 67 kDa proteins. OBJECTIVE: In the present study we have investigated the presence and subcellular location of the 37 kDa and 67 kDa allergen components in various members of the genus Pityrosporum as well as in Candida albicans, Candida parapsilosis and Saccharomyces cerevisiae. METHODS: To detect both cell surface and intracellular expression of the allergens, flow cytometry and confocal laser scanning microscopy (CLSM) were used. The cells were stained with indirect immunofluorescent (IIF) or alkaline phosphatase anti-alkaline phosphatase (APAAP) methods using mouse monoclonal antibodies (MoAbs). RESULTS: Ninety-five per cent of the P. orbiculare (P. ovale) cells cultured for 4 days showed cell surface-binding of the anti-37 kDa MoAb and 88% of the cells bound the anti-67 kDa MoAb when analysed with IIF and flow cytometry. It was found that the members of the genus Pityrosporum (Malassezia), P. pachydermatis and M. sympodialis, expressed the 37 kDa and 67 kDa allergens to a similar extent as did P. orbiculare. Less than 5% of the cells of the genus Candida and S. cerevisiae showed positive staining with the MoAbs. The CLSM revealed that the 37 kDa and the 67 kDa components were located to the cell wall and could not be detected inside the acetone fixed and APAAP stained yeast cells of the genus Pityrosporum. When the yeast cells were cultured for more than 4 days the expression of both allergens decreased significantly. CONCLUSION: All three members of the genus Pityrosporum express the 37 kDa and 67 kDa major allergens on the cell surface, whereas these proteins could virtually not be detected in the Candida genus and S. cerevisiae.

Allergens↗
PubMed1996

Unresponsiveness to 2,4-dinitro-1-fluoro-benzene after treatment with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1 during sensitization.

We have investigated whether hapten-specific unresponsiveness could be induced if the interaction between LFA-1 (CD11a/CD18) and intercellular adhesion molecule-1 (CD54) was disrupted by blocking mAbs given to mice during sensitization with 2,4-dinitro-1-fluorobenzene. An extended period of more than 11 days between the last i.p. injection of mAb and challenge was chosen to ensure that the mAb did not persist in the animals at the time of hapten challenge, as analyzed by flow cytometry and immunohistochemistry. The contact sensitivity response was significantly reduced (p < 0.001) when a combination of mAb FD441.8 against LFA-1 and mAb YNI/1.7.4 against intercellular adhesion molecule-1 was given during the sensitization phase compared with normal rat IgG-treated control animals. Furthermore, the animals were resistant to resensitization to the same hapten. This hyporesponsiveness was hapten specific, since the contact sensitivity reaction of mAb-treated mice to oxazolone was the same as that of normal rat IgG-treated control animals. Together these data indicate that inhibition of LFA-1/intercellular adhesion molecule-1 mediated interactions between APCs and T cells during sensitization induced long term, Ag-specific, hyporesponsiveness of mice to the hapten 2,4-dinitro-1-fluoro-benzene.

Animals↗
PubMed1996

HLA class II is associated with the frequency of glutamic acid decarboxylase M(r) 65,000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus.

Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and -DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1, 23% long-duration type 1, 56% slowly progressive type 1, 3% type 2 patients, and 1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB1*08 allele (100%, Pc < 0.05). GAD65Ab frequencies in DQB1*0302, DQB1*0303, and DRB1*09-positive, long-duration type 1 patients were lower than those in short-duration type 1 patients (14%, 19%, and 20%, Pc < 0.02 compared with short-duration type 1, 90%, 75%, and 71%, respectively), while the frequency varied less in DQB1*04 individuals (44% and 30% in short- and long-duration type 1 patients, respectively). These findings were also observed among patients with DRB1*04, i.e., the haplotype DRB1*0405-DQB1*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short- and long-duration type 1 patients, respectively), while DRB1*04xx-DQB1*0302 showed lower frequency in long-duration type 1 than short-duration (13% and 100%, respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this association might be affected by disease duration in Japanese type 1 patients.

Adolescent↗
PubMed1996

The effect of IFN-gamma on healthy and psoriatic keratinocytes in a skin equivalent model is influenced by the source of the keratinocytes and by their interactions with fibroblasts.

We investigated the effect of interferon-gamma (IFN-gamma) on skin equivalents. Keratinocytes from involved and uninvolved skin from psoriatic subjects and from healthy subjects were grown on preproduced dermal equivalents (DE) containing fibroblasts from healthy skin or psoriatic lesions. Healthy keratinocytes were added when the dermal equivalents were either 22 days (DE(22)) or 37 days old (DE(37)) and psoriatic keratinocytes when the dermal equivalents were 28-52 days old (DE(28-52)). The skin equivalents were cultured for 11 days in a serum-free medium, and then with or without 500 U/ml IFN-gamma for 6 days. The expression of markers associated with differentiation and proliferation were investigated by immunohistochemistry. Differentiation was assessed by computed scores for the expression of cytokeratin 16, involucrin, filaggrin and the receptor for epidermal growth factor. The differentiating effect of IFN-gamma on healthy keratinocytes grown on DE(37) was significantly stronger than on psoriatic keratinocytes grown on DE(28-52). In healthy keratinocytes, the differentiating effect of IFN-gamma was significantly stronger in skin equivalents containing DE(37) than in those containing DE(22). The proliferation rate, i.e. the percentage of Ki-67+ keratinocytes in the basal layer, was studied in healthy keratinocytes grown on DE(22). In these cultures IFN-gamma increased the proliferation rate in the presence of psoriatic fibroblasts but not in the presence of healthy fibroblasts. HLA-DR expression was induced only in healthy keratinocytes grown on DE(22). We conclude that the influence of IFN-gamma epidermal differentiation and proliferation is influenced by the origins of both the keratinocytes and the fibroblasts. These findings suggest that interactions between keratinocytes and fibroblasts might be involved in the pathogenesis of psoriasis.

Adult↗
PubMed1996

Detection of Pityrosporum orbiculare reactive T cells from skin and blood in atopic dermatitis and characterization of their cytokine profiles.

BACKGROUND: Atopic dermatitis (AD) is associated with increased levels of serum IgE, and T-helper (Th) cells are thought to a play role in the pathogenesis. Individuals with AD often develop IgE antibodies against the yeast Pityrosporum orbiculare, a member of the normal cutaneous flora. OBJECTIVE: The role of P. orbiculare in atopic dermatitis was investigated by examining the T-cell reactivity for P. orbiculare. METHODS: Freshly isolated peripheral blood mononuclear cells (PBMC) were isolated from 10 AD patients with serum IgE antibodies against P. orbiculare, and from six healthy controls. The proliferative response after P. orbiculare stimulation, measured by [3H]thymidine incorporation, was examined in the PBMC and in T-cell clones (TCC) obtained from skin and blood of one patient. The cytokine profile of the TCC was determined by enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA) and reverse transcriptase-polymerase chain reaction (RT-PCR) following challenge with either P. orbiculare extract or anti-CD3 antibodies and phytohaemagglutinin. RESULTS: The PBMC response to P. orbiculare was significantly higher in the AD patients than in the control group (P < 0.05). Twenty-nine out of 36 tested TCC derived from one responding patient were reactive for P. orbiculare. The clones were CD2+ and CD4+, except for one CD8+ blood clone. A majority of the TCC derived from lesional skin showed a Th2- or Th2/Th0-like cytokine profile. A co-expression of interleukin-5 (IL-5) mRNA and IL-13 mRNA was detected in five out of six P. orbiculare-reactive clones analysed for their cytokine gene expression with RT-PCR. CONCLUSION: Our data suggest that P. orbiculare can induce a T-cell response in AD patients. The Th2-like profile of P. orbiculare-reactive TCC derived from lesional skin indicates that P. orbiculare may play a role in maintaining IgE-mediated skin inflammation in AD.

Adolescent↗
PubMed1996

Influence of endogenous cortisol on eosinophil function in sensitized pigs: direct measurements of eosinophil peroxidase.

BACKGROUND AND OBJECTIVES: Eosinophils are associated with bronchial asthma, but the role of the eosinophil is not fully understood. This study was initiated in order to study the influence of endogenous cortisol on eosinophil recruitment and activation in allergic inflammation in the lower airways in the pig. METHODS: Polyclonal and monoclonal antibodies against porcine eosinophil peroxidase (EPO) were raised. Detection of eosinophils in blood smears and lung biopsy specimens was achieved using the polyclonal antibody. For determination of porcine EPO in bronchoalveolar lavage (BAL) fluid, a sandwich enzyme-linked immunosorbent assay (ELISA) with a detection limit of 0.15 micrograms/L was developed. No cross-reactivity with porcine myeloperoxidase was found. Pigs that had been actively sensitized with repeated subcutaneous injections of Ascaris suum antigen were acutely challenged with antigen in the lower airways under pentobarbitone anaesthesia. RESULTS: Control animals with plasma cortisol levels of approximately 400 nM did not exhibit infiltration of eosinophils into lung parenchyma or EPO-release in the bronchial lumen within 8 h after challenge. However, in pigs treated with a cortisol-synthesis inhibitor (metyrapone), resulting in plasma cortisol levels of approximately 40 nM, there was a marked eosinophil infiltration into lung tissue at 8 h. Furthermore, EPO levels in BAL fluid were increased in some, although not all, low-cortisol animals. There was no infiltration of eosinophils into skin tissue in these animals. CONCLUSIONS: It is concluded that, after allergen challenge in the lower airways of metyrapone-treated pigs, newly recruited eosinophils infiltrate lung tissue specifically. Furthermore, a cortisol-sensitive release of the eosinophil-derived cationic protein EPO, into the bronchial lumen was established. This is, to our knowledge, the first description of direct measurements of the release of an eosinophil granule protein in a large animal model of allergy.

Animals↗
PubMed1996

Retrieval of leukocyte antigens in paraffin-embedded rat tissues.

We compared the immunohistochemical reactivity of various rat leukocyte antigens in frozen and paraffin-embedded thymus, spleen, abdominal lymph node, liver, and brain tissues of healthy Sprague-Dawley rats, fixed in various fixatives. Immune reactivity after fixation in Methacarn was superior to that of 4% neutral buffered formalin, a mercury-based fixative (B-5), or Carnoy. Microwave (MW) antigen retrieval (AR) enhanced antigen reactivity. Ten of the 11 leukocyte antigens studied could be retrieved in Methacarn-fixed, paraffin-embedded sections with a reactivity comparable to that obtained on frozen sections.

Animals↗
PubMed1996

Patients with psoriasis have elevated levels of serum eosinophil cationic protein and increased numbers of EG2 positive eosinophils in the duodenal stroma.

The occurrence of EG2-positive (EG2+) eosinophils and IgE in biopsy specimens of duodenal mucosa and skin from 39 psoriasis patients was studied, with emphasis on the relation to serum eosinophil cationic protein (ECP), serum IgE and the presence or absence of serum IgA and IgG antigliadin antibodies. Psoriasis patients had significantly elevated serum levels of ECP even after exclusion of five of 37 sera which were Phadiatop positive. The elevated serum ECP was not associated with the presence of IgA or IgG antibodies to gliadin. After exclusion of Phadiatop positive sera the serum IgE values did not differ from those of a group of healthy blood donors. Patients with psoriasis had a pronounced increase of EG2+ cells in their duodenal stroma. Patients without antibodies to gliadin tended to have even more EG2+ cells than those with such antibodies and those with increased duodenal intraepithelial lymphocytes. IgE+ cells were present in most duodenal specimens, and in some specimens there were > 100 IgE+ cells/section. The number of EG2+ cells was increased in lesional skin and, in some patients, also in non-involved skin, but there was a more pronounced increase in EG2 reactivity in the duodenal than in the skin specimens. IgE reactivity was increased both in non-involved and involved skin and was significantly related to the number of IgE-positive cells in the duodenal stroma. The results of this study indicate that the gastrointestinal tract and the eosinophil granulocyte might be involved in psoriasis in a hitherto unknown way.

Adult↗
PubMed1996

Granulocyte function in the airways of allergen-challenged pigs: effects of inhaled and systemic budesonide.

BACKGROUND: Late airways obstruction and eosinophil infiltration after allergen challenge are often seen in human asthma and animal models of allergy. This inflammatory reaction, which may be a link between acute and chronic asthma, is blocked by glucocorticoid pretreatment. However, the role of eosinophils in late airways obstruction and the primary site of action of glucocorticoids, i.e. locally or systemically, have not been fully determined. OBJECTIVES: This study was initiated to find out the role of eosinophils and neutrophils in allergen-induced late airways obstruction in the pig. The effect of pretreatment with budesonide (BUD) given locally or systemically on cellular responses seen within 8 h after allergen challenge was also studied. METHODS: Twenty-five minipigs were actively sensitized with Ascaris suum antigen and challenged under anaesthesia with antigen in the lower airways. Pigs were given BUD as an aerosol (10 micrograms/kg) or an intravenous infusion (5 micrograms/kg) 1 h before allergen challenge. In one group, high doses of BUD (50 micrograms/kg) were infused twice with a 3-h interval before allergen challenge. As a positive control, one group was given the BUD vehicle as an infusion and as a negative control, one group not treated with BUD was given the irrelevant antigen ovalbumin. Eosinophils and neutrophils in lung tissue specimens were detected and levels of eosinophil peroxidase (EPO) and myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) fluid were measured using specific antibodies against porcine EPO and MPO. RESULTS: The number of eosinophils in lung tissue and BAL fluid and the level of EPO in BAL fluid were significantly increased 8 h after A. suum challenge in pigs not treated with BUD. With regard to possible recruitment and activation of neutrophils the only significant finding was an increase in the number of cells in BAL fluid. The eosinophil numbers and the level of EPO in BAL fluid were shown to be decreased by all BUD treatments in all the compartments studied compared to the positive control. However, the number of eosinophils in lung tissue and EPO levels in BAL fluid did not correlate with the magnitude of the late airways obstruction. CONCLUSION: Although eosinophils are present in the bronchial wall and lumen and are apparently activated, a causative relationship between this granulocyte and the late bronchial obstruction could not be established in this model.

Administration, Inhalation↗
PubMed1995

Simultaneous occurrence of rejection and graft-versus-host reaction after allogeneic small bowel transplantation.

Small bowel transplantation may be complicated not only by rejection but also by graft-versus-host reaction (GVHR). So far, little is known about the association between these two immunological reactions, partly because of the lack of standardized, reproducible experimental models for such studies. In this work, a rat model in which GVHR and rejection occur simultaneously was established. When transplanting small bowel grafts from BN donors to Lewis recipients and thereafter treating the grafts locally with the immunomodulating substance LS-2616, a clinically visible GVHR occurred on day 6, at the same time the first signs of rejection became visible. The GVHR was confirmed by immunohistochemical staining for MHC class II-positive cells in liver and ear skin biopsy specimens. An obvious quantitative difference in the number of positive cells in both organs was observed when local treatment was compared with oral LS-2616 treatment or with findings in organs from untreated animals. We conclude that GVHR and rejection are not mutually exclusive and thus may occur simultaneously, and that this pharmacological model might facilitate further studies of the impact of GVHR on graft rejection and recipient survival.

Adjuvants, Immunologic↗
PubMed1995

Alpha 4 integrin directs virus-activated CD8+ T cells to sites of infection.

This article examines the role of VLA-4 in directing lymphocytes to sites of viral infection using the murine lymphocytic choriomeningitis virus infection (LCMV) as the model system. This virus by itself induces little or no inflammation, but in most mouse/virus strain combinations a potent T cell response is induced, which is associated with marked CD8+ cell-mediated inflammation. Two expressions of LCMV-induced inflammation were studied: meningitis induced by intracerebral infection and adoptive transfer of virus-specific delayed-type hypersensitivity. Our previous studies have shown that LCMV infection results in the appearance of activated CD8+ cells with an increased expression of VLA-4. In this study we have compared various T cell high and low responder situations, and these experiments revealed that acute inflammation correlates directly with VLA-4 expression on splenic CD8+ cells. This correlation could be extended to CD4+ and B cells in chronically infected low responder DBA/2 mice. The vascular ligand for VLA-4, VCAM-1, was found to be up-regulated on endothelial cells in sites of inflammation. Finally, preincubation of virus-primed donor cells with mAb to VLA-4 completely blocked the ability to transfer virus-specific, delayed-type hypersensitivity when the donor cells were given i.v., but not when the cells were injected directly into the test site. Co-transfer of CD8-depleted cells with anti-VLA-4-blocked cells did not reveal any cooperation. Taken together, these results indicate that VLA-4 play a critical role in lymphocyte homing during systemic virus infections and are involved in directing virus-specific CD8+ effector cells to sites of infection.

Animals↗
PubMed1995

Macrophages, but not dendritic cells, present collagen to T cells.

Dendritic cells, such as epidermal Langerhans cells, play a crucial role for the antigen-specific priming of T cells. We have addressed the question whether dendritic cells present collagen, a major protein component in tissues through which dendritic cells migrate, i.e. the basement membrane, dermis, and synovial tissue. Langerhans cells, spleen cells and peritoneal macrophages were compared for antigen-presenting capacity using a panel of mouse T cell hybridomas reactive with different determinants on type II collagen, myelin basic protein, ovalbumin and pepsin. Langerhans cells did not present any of the type II collagen determinants, unless the antigen was administered as a 15-mer peptide, but did present myelin basic protein, ovalbumin and pepsin. Spleen cells and peritoneal macrophages, in contrast, presented all type II collagen determinants. This biased antigen presentation was also observed when Langerhans cells were pulsed with antigen in vivo. The inability to present type II collagen is related to the collagen sequence as such, since both native type II collagen, type II collagen alpha chains, as well as a type II collagen determinant incorporated in type I collagen, were not presented by Langerhans cells. In addition, granulocyte/macrophage colony-stimulating factor-expanded blood dendritic cells displayed the same biased antigen presentation, suggesting that the inability to present collagen is not restricted to dendritic cells localized in epidermis. B cell-deficient mice could prime a type II collagen-reactive T cell response, thus excluding B cells as obligatory antigen-presenting cells for the priming of collagen-reactive T cells. We suggest that neither Langerhans cells nor B cells, but macrophages are the primary antigen-presenting cells in the immune response towards type II collagen.

Amino Acid Sequence↗