Biomedical subjects

A Scheynius

Publications and source records attributed to A Scheynius.

At least 91 records · Page 5Linked to original sources

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↗

PubMed1995

Kupffer cell iron overload induces intercellular adhesion molecule-1 expression on hepatocytes in genetic hemochromatosis.

The mechanisms underlying iron-induced liver fibrogenesis in patients with genetic hemochromatosis are poorly understood. We studied signs of Kupffer cell activation and inflammatory responses in liver biopsy specimens obtained from 15 patients with untreated and six patients with treated hemochromatosis. Immunohistochemistry was performed on 11 of the untreated and all treated patients. Three of the untreated patients (20%) had cirrhosis and eight (53%) had fibrosis. None had chronic active hepatitis (CAH). Immunohistochemistry indicated that 55% of the untreated patients had sparse intercellular adhesion molecule-1 (ICAM-1) expression by hepatocytes, and all of these had Kupffer cell iron overload. No ICAM-1 expression was seen by hepatocytes in treated patients or healthy controls. ICAM-1 was strongly expressed by hepatocytes from control patients with inflammatory liver disease. HLA-DR reactivity was seen on sinusoidal cells in all groups, but not on hepatocytes except for two of the control patients with CAH. Twenty-seven percent of the untreated hemochromatosis patients displayed moderate infiltration by CD3-positive lymphocytes. Electron microscopy of samples from untreated hemochromatosis patients showed hypertrophic Kupffer cells containing iron-rich remnants of phagocytosed hepatocytes. Fat-storing cells close to iron-laden hepatocytes contained multiple lipid droplets and adjacent collagen fibril bundles. Thus, in patients with untreated genetic hemochromatosis and Kupffer cell iron overload, hepatocytes occasionally express ICAM-1. In regions with heavy iron overload, Kupffer cell hypertrophy and transition of fat-storing cells are seen. Our findings indicate that release of factors from iron-loaded, activated Kupffer cells is of importance for the transformation of fat-storing cells and increased collagen deposition seen in genetic hemochromatosis.

Adult↗

PubMed1995

Not only Th2 cells but also Th1 and Th0 cells express CD30 after activation.

To investigate whether the CD30 molecule, expressed only by a minority of T and B cells, defines a subtype of T helper cells, Pityrosporum orbiculare-specific CD4+ T cell clones were assessed for CD30 protein and gene expression. The clones were defined as Th1, Th0, and Th2 according to their cytokine mRNA profile detected by reverse transcription PCR (RT-PCR). The kinetics of CD30 expression after OKT3 (anti-CD3) stimulation was analyzed by flow cytometry, immunocytochemistry, and RT-PCR. OKT3 activation induced a high expression of CD30 in cells of both Th1 and Th0 as well as Th2 type after 1-3 days. A difference between the clones was noted in that the Th2 clones remained highly positive in CD30 expression, whereas expression in the other clones started to decline from day 3. These data indicate that CD30 is expressed in activated CD4+ T cells of all three subtypes, and that the expression is sustained in Th2 cells.

Base Sequence↗

PubMed1995

Ketoconazole in atopic dermatitis: therapeutic response is correlated with decrease in serum IgE.

The prevalence of specific IgE antibodies to the yeasts Pityrosporum orbiculare and Candida albicans was investigated in adult patients with atopic dermatitis (AD) or with seborrhoeic dermatitis and in healthy controls by means of the radioallergosorbent test (RAST). Of 63 AD patients, 28 (44%) had IgE antibodies to P. orbiculare and 21 (33%) to C. albicans. This is highly significant, since no antibodies were found in sera from other patients or controls. With the intention to treat, 20 patients with AD and a positive RAST to P. orbiculare were given ketoconazole 200 mg daily for 2 months and 200 mg twice weekly for further 3 months. The clinical scores improved during treatment with a reduction in the levels of specific IgE to P. orbiculare and total serum IgE. However, there were no correlations between clinical score and serum levels of P. orbiculare-specific IgE. C. albicans-specific IgE, on the other hand, correlated both with clinical score and with total serum IgE.

Adolescent↗

PubMed1995

Proliferation and interferon-gamma receptor expression in psoriatic and healthy keratinocytes are influenced by interactions between keratinocytes and fibroblasts in a skin equivalent model.

Epidermal-dermal interactions were studied in a skin equivalent model. Six combinations of keratinocytes and fibroblasts from healthy and psoriatic skin were used. TPA (12-O-tetradecanoylphorbol-13-acetate) was used to determine whether the expression of the IFN-gamma receptors in keratinocytes was related to epidermal differentiation and proliferation. These phenomena were assessed by immunohistochemistry. In all epidermal outgrowths, the epidermal growth factor receptor was expressed throughout the epidermis, cytokeratin 16 suprabasally, and filaggrin and involucrin in its superficial part. The IFN-gamma receptor was expressed throughout the epidermis, but was unevenly distributed. The expression of the IFN-gamma receptor was quantified by confocal laser scanning microscopy both in the whole of epidermis and in areas with the strongest intensity. The total amount varied to a minor degree in the epidermal outgrowths of different origins and was unaffected by TPA. In high-intensity areas interactions between keratinocytes and fibroblasts did influence the amount of IFN-gamma receptor expression and TPA decreased the expression by 13%. There was no correlation between the proliferation rate and the expression of the IFN-gamma receptor. Psoriatic and healthy keratinocytes were equally well differentiated in the skin equivalents. The interferon-gamma receptor was similarly expressed under these conditions. The growth rate, assessed by Ki-67-positive nuclei in the basal layer, was highest in healthy keratinocytes. Keratinocytes from psoriatic lesions increased their growth rate when cocultured with psoriatic fibroblasts compared with normal ones, indicating that fibroblasts may be of importance for epidermal hyperproliferation in psoriatic lesions.

Adult↗

PubMed1995

Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects.

To explore the pruritogenic and inflammatory effects of cytokines, a single dose of 20 micrograms recombinant human interleukin-2 was injected intradermally into eight patients with atopic dermatitis and eight healthy controls. The study was double-blind and randomized with glucose as a negative control. The effects were evaluated by recording local itch and erythema over 72 h and by examining skin biopsies taken at 24 h and 72 h. In patients and controls, interleukin-2 provoked a low-intensity local itch with maximal intensity between 6 h and 48 h and erythema with maximal extension between 12 h and 72 h. In the atopic dermatitis patients, these reactions tended to appear earlier and were less pronounced than in the healthy controls. Interleukin-2 induced dermal mononuclear cell infiltrates consisting mainly of CD3+ cells. A majority of the T cells were CD4+. The number of dermal CD25+, HLA-DR+ and ICAM-1+ cells was also increased at the interleukin-2 induced spongiosis and exocytosis as well as HLA-DR+ and ICAM-1+ keratinocytes. The microscopic findings tended to be more prominent at 72 h than at 24 h in both groups, but with a somewhat slower onset in the atopic dermatitis patients. In conclusion, a single intradermal injection of interleukin-2 induced local itch, erythema, dermal T-cell infiltrates, spongiosis, exocytosis and activation of keratinocytes both in atopic dermatitis patients and in healthy controls.

Adult↗

PubMed1995

Virus-activated T cells regulate expression of adhesion molecules on endothelial cells in sites of infection.

To study the role of cell adhesion molecules in the fatal CD8+ T-cell mediated meningitis which is induced by intracerebral infection with lymphocytic choriomeningitis virus, the expression of relevant molecules on inflammatory cells and local endothelium was analyzed immunohistochemically. Most inflammatory cells were strongly positive for LFA-1, VLA-4, Pgp-1 and ICAM-1. Expression of ICAM-1 and VCAM-1 was upregulated on the endothelial cells in immunocompetent mice, but not in T-cell deficient nude mice. Analysis of mice deficient in either CD4+ or CD8+ T cells, revealed that not only was the inflammatory reaction dependent on the presence of CD8+ cells, but these cells also appeared to be required for maximal upregulation of ICAM-1 and VCAM-1 on the endothelial cells. These results indicate that virus-specific CD8+ T cells are crucially involved in regulating the inflammatory reaction through effects on endothelial expression of adhesion molecules.

Animals↗

PubMed1995

IgE, IgE receptors, and other immunocytochemical markers in atopic and nonatopic patients with vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) often is associated with atopy but a considerable part of the patients lack evidence of specific hypersensitivity. An immunocytochemical study was undertaken with the aim of detecting possible differences in the tissue inflammatory response between atopic and nonatopic subjects with VKC. METHODS: Conjunctival biopsy specimens from six atopic and three nonatopic subjects with VKC (age range, 7-17 years) and eight healthy control subjects (age range, 3-15 years) were analyzed with a panel of monoclonal and polyclonal antibodies. RESULTS: No distinct differences in cell counts between atopic and nonatopic subjects with VKC were observed. Vernal keratoconjunctivitis specimens as a whole showed higher counts than control specimens for CD3+, CD4+, HLA-DR+, CD38+, EG2+, CD68+, IgE+, FC epsilon RI+, IgA+, IgG+, and IgM+ cells in the substantia propria; and for CD1a+, IgE+, and EG2+ cells in the epithelium. CONCLUSIONS: Because the number of cells expressing CD4, EG2, IgE, and the high-affinity receptor for IgE, all of which are considered relevant in infiltrates of allergic conditions, were similar in atopic and nonatopic subjects, the authors conclude that the role of allergen-specific IgE sensitization in the pathogenesis of VKC remains unclear.

Adolescent↗

PubMed1995

Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin.

In a screening study concerning IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA, respectively) in psoriasis, raised levels of IgA and AGA were found to be more common than in a reference group. To determine whether elevated AGA levels were associated with an increased number of intraepithelial lymphocytes, 33 patients with IgA AGA (n = 28) or IgG AGA (n = 5) values above 90% of the reference values (> 50 units/ml IgA AGA and < 12 units/ml IgG AGA) underwent gastroduodenoscopy and duodenal biopsy in a prospective study. For comparison, six patients with low levels of both IgA AGA and IgG AGA were included. Five biopsy specimens were taken in each patient. Paraffin-embedded specimens were examined with regard to the degree of intraepithelial lymphocyte infiltration, and scored from 0 to 3. Biopsy specimens with a score of 0 had one mononuclear cell or less per four epithelial cells. The specimens were also examined with regard to the presence of intraepithelial CD3+ T lymphocytes and gamma/delta+ T lymphocytes. In the six patients with low IgA AGA and low IgG AGA, the biopsy score was 0. Fourteen of the 33 patients with raised AGA had a score of > or = 1; of these, 12 had raised IgA AGA and two had slightly raised IgG AGA. Two of the patients with raised IgA AGA had partial villous atrophy, but the majority had normal villous architecture. There was a significant correlation both between the biopsy score and the number of intraepithelial CD3+ cells and between the score and the number of intraepithelial gamma/delta+ positive T lymphocytes. The serum IgA AGA levels were significantly correlated with the duodenal biopsy score, the number of intraepithelial gamma/delta+ T lymphocytes, and the number of CD3+ intraepithelial T lymphocytes. Most patients had no, or only mild, gastrointestinal symptoms. Of the 14 patients with biopsy scores > or = 1, seven had severe psoriasis and five moderately severe psoriasis, whereas only two had mild psoriasis. There was no relationship between the duodenal score and haemoglobin, folate, whole blood selenium or serum zinc levels. Some of these patients improve on a gluten-free diet, but it is still too early to draw any definite conclusions concerning the type of relationship between the skin lesions, the increased number of intraepithelial lymphocytes in the duodenal mucosa and gluten hypersensitivity.

Adult↗

PubMed1995

Localization of major allergens in the dust mite Lepidoglyphus destructor with confocal laser scanning microscopy.

The dust mite Lepidoglyphus destructor is the dominating source of allergens giving rise to asthma and rhinitis among farmers. In a previous study of the localization of allergens in L. destructor we demonstrated that the 39 kDa allergen is associated with digestion. Here we describe the localization of the principal 15 kDa allergen and the high molecular weight allergen complex (79 and 93 kDa) in L. destructor with confocal laser scanning microscopy (CLSM). Cryostat-cut sections of mite bodies and faecal pellets were probed with mouse monoclonal antibodies (MoAbs) raised against the allergens. The 15 kDa allergen disclosed labelling of the mite body and most of the faecal pellets but left the exoskeleton unlabelled. The binding was widespread, and most intense in the mouth region. However, some staining was also observed around the gastrointestinal tract. In contrast, the 79 and 93 kDa allergen complex stained the exoskeleton and the front part of the mite. Interestingly, we detected no labelling of the faecal pellets with the MoAb against the 79/93 kDa allergen. The study indicates that the 15 kDa allergen is associated with the digestive tract whereas the function of the 79 and 93 kDa allergen complex remains to be elucidated.

Allergens↗

PubMed1995

Influence of culture period on the allergenic composition of Pityrosporum orbiculare extracts.

BACKGROUND: Previous characterization studies of Pityrosporum orbiculare allergens have led to contradictory results. In immunoblotting studies a range of IgE-binding proteins of 10-100 kDa have been identified. In another study, however, the IgE-binding structures were claimed to be associated with high-molecular-weight polysaccharides or glycoproteins, presumably mannans or mannoproteins. OBJECTIVE: In the present study the reasons for these discrepancies were investigated. METHODS: P. orbiculare preparations were compared in IgE ELISA and IgE-inhibition ELISA, as well as in immunoblotting with sera from atopic dermatitis patients. RESULTS: It was inferred that variations in the period of in vitro culture of P. orbiculare constituted the most important factor determining the different compositions of the resulting yeast cell extracts. After 2 days of culture a wide range of allergenic proteins was present but upon more prolonged culture (> 4 days) most proteins of 10-100 kDa were lost. Accordingly, the protein concentration of the extracts gradually declined from 40% to 25% between days 4 and 15 of culture. On the other hand, the carbohydrate content remained fairly constant (approximately 30%). Using inhibition ELISA it was demonstrated that the high-molecular-weight glycoproteins or polysaccharides presumably involved in most of the IgE-binding capacity in extracts from old cultures, were also present in comparable concentrations in all extracts tested, even after culture for only 2 or 4 days. CONCLUSION: Preparations obtained from the exponential phase of yeast cultures (2-4 days old), should preferably be used in studies of the IgE response to P. orbiculare.

Allergens↗

PubMed1995

Interferon-alpha production and tissue localization of interferon-alpha/beta producing cells after intradermal administration of Aujeszky's disease virus-infected cells in pigs.

Intradermal administration of glutaraldehyde-fixed Aujeszky's disease virus (ADV) infected autologous or allogeneic cells resulted in the induction of an interferon (IFN)-alpha response in pigs. Using a sensitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), IFN-alpha was detected in blood at 8 and 24 h after injection of ADV-infected cells. In parallel, by means of in situ hybridization, IFN-alpha/beta mRNA containing cells were demonstrated in regional lymph nodes. Occasional IFN-alpha/beta mRNA positive cells were also seen in injected dermal areas, but not in contralateral lymph nodes, spleen, bone marrow, blood or liver. The ability of leucocytes in whole blood cultures to produce IFN-alpha upon stimulation by ADV was markedly diminished 3-7 days after intradermal injection of ADV-infected cells. In contrast, cultures of purified peripheral blood mononuclear cells (PBMC) had intact IFN-alpha responses. Further, serum from ADV-injected pigs inhibited the in vitro ADV-induced IFN-alpha responses in PBMC from control pigs, most likely due to the demonstrated presence of anti-ADV antibodies. We suggest that the IFN-alpha/beta producing cells in lymph nodes may participate in the development of antiviral immunity and could be equivalent to Natural IFN-alpha/beta producing (NIP) cells.

Animals↗

PubMed1995

Lymphocytic choriomeningitis virus infection is associated with long-standing perturbation of LFA-1 expression on CD8+ T cells.

Flow cytometric analysis of splenocytes from mice infected with lymphocytic choriomeningitis virus revealed marked and long-standing up-regulation of LFA-1 expression on CD8+, but not on CD4+ T cells. Appearance of CD8+ T cells with a changed expression of adhesion molecules reflected polyclonal activation and expansion which was demonstrated not to depend on CD4+ T cells or their products. Cell sorting experiments defined virus-specific CTL to be included in this population (LFA-1hiMEL-14lo), but since about 80% of splenic CD8+ T cells have a changed phenotype, extensive bystander activation must take place; this is indicated also by the finding that CD8+LFA-1hi cells transiently express several markers of cellular activation, e.g. transferrin receptor, IL-2R alpha and beta. Analysis of cells from the cerebrospinal fluid of mice infected intracerebrally showed that virtually all T cells present belonged to the CD8+LFA-1hi subset and, correspondingly, the ligand ICAM-1 was found to be up-regulated on endothelial cells in the inflamed meninges. Preincubation of LCMV-primed donor splenocytes with anti-LFA-1 markedly inhibited the transfer of virus-specific delayed-type hypersensitivity to naive recipients. Together, these findings indicate that up-regulation of LFA-1 expression is a critical factor involved in directing activated CD8+ T cells to sites of viral infection.

Animals↗