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J Reimann

Publications and source records attributed to J Reimann.

At least 109 records · Page 6Linked to original sources
PubMed1995

[Cogan I syndrome: too often detected too late? A contribution to early diagnosis of Cogan I syndrome].

BACKGROUND: Cogan's syndrome is an uncommon disease characterized by ocular inflammation, vestibuloauditory dysfunction and symptoms of systemic disease. The etiology is unknown, however there is evidence for an autoimmune pathogenesis. The "typical" Cogan's syndrome presents as bilateral interstitial keratitis and progressing vestibuloauditory dysfunction. The presence of other inflammatory manifestations in addition of keratitis has been termed as "atypical" Cogan's syndrome. PATIENTS: We report on six patients presenting with typical as well as atypical ocular manifestations between 1982 and 1994. Typically, the illness was accompanied by systemic symptoms. Each patient had audiovestibular involvement, that was the initial presentation in 4 cases. Vestibular dysfunction often preceded hearing loss. Five of our patients not only presented with keratitis but also demonstrated signs of ocular inflammation diagnosed as scleritis or episcleritis. In two patients these ocular symptoms were the first signs of Cogan's syndrome, recurred periodically and did not respond to corticosteroids. RESULTS: In 3 patients that were diagnosed early and treatment with corticosteroids was initiated early, hearing could be stabilized, in the remaining patients total bilateral deafness could not be prevented. CONCLUSION: The importance of being aware that vestibuloauditory dysfunction may occur in patients with ocular inflammation, and the fact that early immunotherapy may prevent the risk of deafness, has to be emphasized.

Adolescent↗
PubMed1995

DNA-mediated immunization in mice induces a potent MHC class I-restricted cytotoxic T lymphocyte response to the hepatitis B envelope protein.

The particulate form of the major envelope or surface (S) protein of hepatitis B virus (HBV) can be taken up by antigen-presenting cells and processed for class I presentation as an exogenous protein. We have used several DNA plasmid vectors expressing the HBV envelope proteins to determine whether these sequences are able to induce cytotoxic T lymphocyte (CTL) responses in BALB/c mice after intramuscular DNA injection. A potent and specific induction was obtained, which can be detected ex vivo using either specific or nonspecific (interleukin-2) stimulation in cell culture, and the DNA-primed CTL responses are stronger than those obtained with protein injection with either stimulation protocol. The CTL response induced by DNA-based immunization is both canonical and highly specific as indicated by the nature of the epitope presented (amino acids 28-39), the class I allele used (Ld), and the T lymphocytes involved (CD8+). The CTL response is initiated between 3 and 6 days after DNA injection. By 6-12 days after a single DNA injection, ex vivo cytolytic activity is nearly maximal, and similar high levels of activity can still be detected 4 months after injection. The possibility is discussed that the unusual mode of delivery of the antigen to the immune system provided by in situ expression might allow HBV envelope antigen to be taken up and processed for class I presentation by in situ expression might allow HBV envelope antigen to be taken up and processed for class I presentation as an exogenous protein in addition to activating potentially the classical endogenous pathway.

Animals↗
PubMed1995

Regional specialization of intraepithelial T cells in the murine small and large intestine.

We investigated intraepithelial T cells from the small intestine, SI (jejunum, ileum) and the large intestine, LI (colon) of euthymic (BALB/c, H-2d; C.B-17+/+, H-2d; C57BL/6, H-2b) and athymic (C57BL/6 nu/nu; BNX bg/bg nu/nu xid/xid) mice. From individual euthymic and athymic mice, 7 x 10(6) intraepithelial lymphocytes (IEL) per mouse were isolated from the SI. Ten-fold lower numbers of IEL were obtained from the LI epithelium (4 x 10(5) IEL per mouse). Thymus-dependent and -independent T cells represented > 80% of SI-IEL but the fraction of T cells was reduced from 20% to 40% in LI-IEL. In euthymic mice, alpha beta T cells predominated in SI-IEL and in particular in LI-IEL populations, while SI-IEL and LI-IEL populations of athymic mice contained predominantly gamma delta T cells. The intraepithelial T cell subset distribution was different in SI versus LI: mainly CD8+ T cells were present in the SI, but a large CD4+ T cell subset was present in the LI. 'Double positive' CD4+ CD8 alpha+ T cells were present mainly in the SI epithelium but were rare in the LI epithelium. In euthymic as well as athymic mice, T cells expressing the homodimeric CD8 alpha alpha isoform predominated in the SI epithelium, while T cells expressing the heterodimeric CD8 alpha beta isoform predominated in the LI epithelium. LI-derived TCR alpha beta+ IEL displayed the CD2+ CD28+ LPAM-1/2- M290+ phenotype, and a fraction of them expressed the L-selectin LECAM-1. In contrast, a large fraction of TCR alpha beta+ SI-IEL was CD2- CD28- LPAM-1/2- M290+ and LECAM-1-. RAG-1/2 expression was detectable by RT-PCR in IEL from the SI but not the LI. Striking differences in phenotype were thus apparent between thymus-dependent and thymus-independent T cells in the epithelial layer of the jejunum/ileum and the colon of the mouse.

Animals↗
PubMed1995

Lamina propria T cell subsets in the small and large intestine of euthymic and athymic mice.

We investigated lamina propria T cells from the small intestine (jejunum/ileum) and the large intestine (colon) of euthymic (BALB/c, C.B-17, C57BL/6) and athymic (C57BL/6 nu/nu; BNX bg/bg nu/nu xid/xid) mice. CD3+ T cells represented about 40% of the lamina propria lymphocytes (LPL) from the small or the large intestine of euthymic mice, and 20-30% of the LPL populations from the small or large intestine of athymic mice. In the lamina propria T cell population of the small intestine, 85% were of the alpha beta lineage in euthymic mice, but only 40% were of the alpha beta lineage in athymic mice. T cells of the gamma delta lineage were thus more frequent than T cells of the alpha beta lineage in the intestinal lamina propria T cells of extrathymic origin. CD4+ T cells represented 40% of the lamina propria T cells in the small as well as in the large intestine of euthymic mice, and 20-30% of the T cells in the lamina propria of the nude mouse gut. In euthymic mice, 40% of the T cells in the small intestine lamina propria, and 30% of the T cells in the colonic lamina propria were CD8+. In intestinal lamina propria T cell populations of athymic mice, the CD8+ T cell population was expanded. Most (60-70%) CD8+ T cells in the lamina propria of the small and the large intestine of euthymic and athymic mice expressed the homodimeric CD8 alpha + beta- form of the CD8 coreceptor. A fraction of 15-20% of all CD3+ T cells in the lamina propria of the small and the large intestine of euthymic and athymic mice were 'double negative' CD4- CD8-. A large fraction of the TCR alpha beta + T cells in the colonic lamina propria (but not in the small intestine lamina propria) of euthymic mice expressed the CD2 and the CD28 costimulator molecules, the adhesion molecule LECAM-1 (CD62 L), and could be activated in vitro by CD3 ligation. These data reveal a considerable heterogeneity in the surface phenotype and the functional phenotype of murine lamina propria T cells.

Animals↗
PubMed1995

Nucleic acid vaccination primes hepatitis B virus surface antigen-specific cytotoxic T lymphocytes in nonresponder mice.

The efficiency of different vaccination techniques to prime in vivo major histocompatibility complex class I-restricted murine cytotoxic T-lymphocyte (CTL) precursors to hepatitis B virus small surface antigen (HBsAg) was investigated. Mice were immunized either by injection of a low dose of recombinant HBsAg protein preparations (native HBsAg particles or denatured HBsAg monomers) without adjuvants, by infection with recombinant vaccinia virus carrying an HBsAg-encoding gene, or by intramuscular transfer of plasmid DNA encoding HBsAg under appropriate promoter control. In H-2d mice, an Ld-restricted, S28-39-specific CTL response was efficiently primed by all alternative vaccination techniques tested, but the most potent priming of class I-restricted CTL to HBsAg in vivo was observed with DNA immunization. Priming of anti-HBsAg CTL in H-2b mice was not detectable after infection with a recombinant vaccinia virus or after injection with exogenous recombinant HBsAg preparations. After DNA immunization, however, both Kb- and Db-restricted CTL reactivity to HBsAg emerged in H-2b mice. Hence, nucleic acid immunization revealed class I-restricted CTL responsiveness to HBsAg in a mouse strain previously considered to be a nonresponder at the CTL level. These results demonstrate that the simple technique of nucleic acid immunization not only is extremely efficient but also reveals an extended spectrum of potentially immunogenic epitopes of protein antigens.

Animals↗
PubMed1995

Stable engraftment of human female genital mucous membrane xenografts on SCID mice.

We developed a model in which full-thickness human genital mucous membranes (fallopian tubes, endometrium) were heterotopically xenografted into the skin of severe combined immunodeficient (SCID) mice. The transplanted tissue retained its human phenotype for at least 4 weeks including the glandular epithelium, the lamina propria, and main parts of the grafted vessels. By using an occlusive chamber filled with covering phosphate-buffered saline we created a system that protected the moist human epithelial surface. This system will allow the study of the interaction of test substances, or of invasive, pathogenic microorganisms, with epithelial cells and other cellular components of the human genital mucosa under in vivo conditions.

Animals↗
PubMed1994

CD8+ T lymphocyte-mediated antiviral immunity in mice as a result of injection of recombinant viral proteins.

A major portion of the nucleoprotein (amino acids 67 through 300) and the glycoprotein-2 of lymphocytic choriomeningitis (LCM) virus were synthesized by using recombinant technology and were injected together with SDS twice in portions of 5 micrograms into BALB/c mice. As evidenced by diminished replication of LCM challenge virus, both proteins induced antiviral immunity, which was comparable in extent with the immunity caused by infection with LCM vaccinia recombinant viruses. Primed LCM-viral CTLs could not be demonstrated in these mice by culturing splenocytes in the presence of LCM virus, and Abs appeared slowly and in low quantities; but, after injection of large infectious doses, CTLs appeared faster and in higher numbers than in mice not previously treated with viral proteins. Depletion of CD8+ cells, but not of CD4+ cells, by treatment of mice with mAb abolished the antiviral immunity, demonstrating that protection was mediated by CD8+ T lymphocytes. Absence of CD4+ T lymphocytes before and during the period of immunization did not measurably affect the animals' antiviral immune status, indicating that activation of the CD8+ T lymphocytes was not dependent on help by CD4+ cells.

Amino Acid Sequence↗
PubMed1994

Immunization with soluble hepatitis B virus surface protein elicits murine H-2 class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo.

Immunization with soluble proteins only rarely induces a specific response of CD8+ CTL. We describe experiments that demonstrate the efficient and specific in vivo priming of CTL in BALB/c mice immunized with soluble hepatitis B virus (HBV)-derived surface (S) protein. A single (s.c., i.p. or i.v.) injection of a low dose (30 ng to 3 micrograms per mouse) of recombinant S protein particles without adjuvants induced a CTL response. This specific cytotoxic response was read out against a panel of different S protein-expressing transfected mouse cell lines. Effector cells of this response were Ld-restricted, CD3+ CD4- CD8+ CTL. H-2d/Ld+ (BALB/c, C.B-17) mice were responders; H-2d/Ld- (dm2) mutant mice and H-2b (C57BL/6) mice were nonresponders. Injections of various dosages of a S protein-derived, immunogenic, synthetic peptide into BALB/c mice by various routes did not prime CTL. After incorporation of S protein particles into IFA or aluminum hydroxide, these protein Ag lost their ability to specifically stimulate CTL in vivo. After priming of mice with S protein emulsified in IFA or adsorbed to aluminum hydroxide boost injections with native S protein particles were inefficient in stimulating a specific CTL response. These findings are of relevance for the design of synthetic subunit vaccines for which specific stimulation of CD8+ T effector functions is desired.

Adjuvants, Immunologic↗
PubMed1994

Selective stimulation of murine cytotoxic T cell and antibody responses by particulate or monomeric hepatitis B virus surface (S) antigen.

In the murine system, we tested in vivo the immunogenicity of different preparations of the yeast-derived surface antigen (S-antigen or S-protein) of hepatitis B virus (HBV). Native S-protein molecules self-assemble into stable 22-nm particles. BALB/c mice immunized with low doses of native S-particles without adjuvants efficiently generated an H-2 class I-restricted CD8+ cytotoxic T lymphocyte (CTL) response, and developed easily detectable serum antibody titers against conformational determinants of the native S-particle or linear epitopes of the denatured S-protein. Disruption of S-particles with sodium dodecyl sulfate and beta-2-mercaptoethanol generated p24 S-monomers. Injection of an equal dose of S-monomers into mice efficiently primed CTL, but did not stimulate an antibody response against conformational or linear epitopes of the native or denatured S-protein. In vivo priming of CTL by S-particles or S-monomers required "endogenous" processing of the antigen because the injection of an equimolar (or higher) dose of an antigenic, S-derived 12-mer peptide into mice did not prime CTL. Native (particulate) or denatured (monomeric) S-antigen injected with mineral oil (incomplete Freund's adjuvant) or aluminum hydroxide failed to stimulate a CTL response. Hence, different preparations can be produced from a small protein antigen which specifically stimulate selected compartments of the immune system.

Amino Acid Sequence↗
PubMed1994

Vaccination with T cell receptor peptides primes anti-receptor cytotoxic T lymphocytes (CTL) and anergizes T cells specifically recognized by these CTL.

We selected three peptides from the germ-line sequence of the V beta 8.2 and J beta 2.3 gene segments of the murine T cell receptor for antigen (TCR) which contained putative Kd- and Ld-restricted epitopes. Immunization of BALB/c (H-2d) mice with the V beta 8.2(67-90) 23-mer peptide 1 as well as the 15-mer V beta 8.2(95-108)-peptide 2 efficiently primed specific CD8+ cytotoxic T lymphocyte (CTL) responses in vivo against natural TCR-V beta 8.2 epitopes. V beta 8.2+ T cells were not deleted in TCR peptide-immunized mice because the fractions of V beta 8.2+ CD4+ and V beta 8.2+ CD8+ T cells in spleen and lymph nodes were not altered. The proliferative response of V beta 8.2+ T cells to stimulation by monoclonal antibody F23.2 was selectively suppressed (by 60-80%) in peptide-immunized BALB/c mice, indicating partial anergy of this T subset. Immunization of BALB/c mice with the J beta 2.3-derived peptide 3 stimulated a CD8+ CTL response against a class I-restricted epitope within this J beta segment that was also generated during natural "endogenous" processing of this self antigen. These data confirm the predictive value of major histocompatibility complex class I allele-specific motifs. The described experiments indicate that TCR peptide-primed CD8+ CTL recognize class I-restricted, natural V beta/J beta-TCR epitopes. Such anti-TCR CTL may, thus, operate in V beta-specific immunoregulation of the T cell system suppressing their functional reactivity without deleting them.

Amino Acid Sequence↗
PubMed1994

Peptide transporter-independent, stress protein-mediated endosomal processing of endogenous protein antigens for major histocompatibility complex class I presentation.

The peptide transporter-defective cell line RMA-S expressing the wild-type simian virus 40 large T antigen (wtT-Ag) from a transfected gene did not present two well-defined, H-2 class I (Db)-restricted epitopes of T-Ag to cytotoxic T lymphocytes (CTL). Hence, "endogenous" processing and presentation of the wtT-Ag depended on a functional peptide transporter heterodimer. In contrast, both T-Ag epitopes were efficiently presented to CTL by transfected RMA-S cells expressing a truncated, cytoplasmic T-Ag variant (cT-Ag) or a karyophilic, amino-terminal 272-amino acid T-Ag fragment. Transporter-independent "endogenous" processing of mutant T-Ag molecules correlated with their association with the constitutively expressed heat shock protein 73 (hsp73). Class I-restricted presentation of both epitopes processed from these hsp73-associated protein antigens was sensitive to NH4Cl and chloroquine. These data indicate that selected intracellular proteins access an alternative, hsp73-mediated pathway for class I-restricted presentation that operates independent of peptide transporters in an endosomal compartment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Injection of detergent-denatured ovalbumin primes murine class I-restricted cytotoxic T cells in vivo.

Complex adjuvant formulations have been used to introduce soluble protein antigens into the "endogenous" processing pathway and hence to elicit specific, major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) responses. We tested if simple modifications of a model protein antigen, i.e. ovalbumin (OVA), can render it immunogenic for murine class I-restricted CTL when injected into mice in soluble form. Injection of 1-100 micrograms native OVA into C57BL/6 (H-2b) mice did not stimulate a class I-restricted CTL response. In contrast, immunization of mice with 0.5 to 10 micrograms sodium dodecyl sulfate (SDS)- or deoxycholate (DOC)-denatured OVA efficiently primed CD8+ CTL specific for the well-characterized Kb-restricted OVA257-264 epitope. Gel-purified SDS-denatured OVA devoid of protein fragments and excess detergent efficiently stimulated a specific CTL response in vivo. OVA preparations denatured by heat or urea treatment were not immunogenic for murine CTL. Injection of non-treated or detergent-treated, antigenic OVA257-264 peptide into mice did not elicit a CTL response. Thus, denaturation of OVA by simple detergents such as SDS or DOC dramatically enhances its immunogenicity for class I-restricted CTL but not all modes of denaturation are equally effective.

Animals↗
PubMed1994

Gut-homing CD4+ T cell receptor alpha beta+ T cells in the pathogenesis of murine inflammatory bowel disease.

We studied which T cell subsets from the gut-associated lymphoid tissue (GALT) can migrate out of the gut mucosa and repopulate GALT compartments of an immunodeficient (semi)syngeneic host. Many distinct lymphocyte subsets were found in GALT of immunocompetent H-2d (BALB/c, BALB/cdm2, C.B-17+/+) mice. No antigen receptor-expressing lymphoid cells were found in GALT of congenic C.B-17 scid/scid (scid) mice. The heterotopic transplantation of a full-thickness gut wall graft from the ileum or colon of immunocompetent (C.B-17+/+, BALB/cdm2) donor mice onto immunodeficient scid mice selectively reconstituted a CD3+ T cell receptor alpha beta+ CD4+ T cell subset. CD4+ cells of this subset expressed the surface phenotype of mucosa-seeking, memory T cells. In the immunodeficient scid host, this gut-derived CD4+ T cell subset was found in spleen, peritoneal cavity, mesenteric lymph nodes (LN), epithelial layer and lamina propria of the small and large intestine, but not in peripheral LN. Scid mice heterotopically transplanted with gut from a congenic, immunocompetent donor developed clinical and histological signs of inflammatory bowel disease (IBD). Hence, the selective repopulation of GALT compartments with CD4+ T cells from normal GALT plays an essential role in the pathogenesis of IBD in an immunodeficient host.

Animals↗
PubMed1994

Antibody and cytotoxic T-cell responses to soluble hepatitis B virus (HBV) S antigen in mice: implication for the pathogenesis of HBV-induced hepatitis.

Immune responses to components of hepatitis B virus (HBV) are assumed to play an essential role not only in the elimination of the virus but also in the pathogenesis of HBV-induced hepatitis. Protective humoral immunity to HBV is mediated by immune responses to HBV surface antigen (HBsAg). It is important to know which HBsAg preparations induce which type of cellular and humoral immune responses under which immunization conditions. We studied in BALB/c mice the humoral (antibody) response and the class I-restricted cytotoxic T-lymphocyte (CTL) response to different preparations of HBsAg particles: recombinant, small protein particles; plasma-derived, mixed particles formed by large, medium, and small surface proteins; and different preparations of recombinant, mixed particles formed by large and small surface proteins. Specific antibody levels appeared in the sera of immunized mice 2 to 3 weeks after immunization and were correlated with the antigen dose used for priming. HBsAg-specific antibody levels were enhanced by boost injections or by adsorbing the antigen to aluminum hydroxide. Injected in particulate form without adjuvants in the dose range of 0.1 to 10 micrograms per mouse, all HBsAg preparations tested efficiently primed specific CD8+ CTL of defined restriction and epitope specificity. Specific CTL reactivity was detectable from 5 days to more than 4 months postimmunization. In the dose range tested, it was independent of the antigen dose used for immunization and not enhanced by repeated boost injections. CTL were not elicited by HBsAg adsorbed to aluminum hydroxide. We have thus defined conditions under which HBsAg induced preferentially either a cellular immune response or a humoral immune response. These findings may be relevant for the interpretation of HBV-associated immunopathologic phenomena.

Adjuvants, Immunologic↗
PubMed1994

Alternative processing pathways for MHC class I-restricted epitope presentation to CD8+ cytotoxic T lymphocytes.

CD8+ cytotoxic T lymphocytes (CTL) mediate protective immunity against many intracellular pathogens. New generation vaccines that exploit the potential of recombinant protein technology have to meet the challenge to identify immunodominant antigen systems of the pathogen of interest, to produce these antigens in recombinant form, and to find ways to selectively deliver them to the compartments of the specific immune system that mediate the protective responses. Immunization with soluble protein antigens usually primers CD4+ T cells but not CD8+ T cells because of the stringent requirements for 'endogenous processing' for major histocompatibility complex (MHC) class I-restricted epitope presentation to CD8+ CTL. This rule is not absolute because priming of class I-restricted CTL by soluble, recombinant viral protein antigens injected without adjuvants has been reported in various antigen systems. An understanding of the cell biology of alternative pathways of protein antigen processing for MHC class I-restricted epitope presentation is emerging. We describe subcellular sites, alternative peptide transport mechanisms, and alternative modes of MHC class I molecule recycling that allow different modes of peptide loading of class I molecules. Experimental evidence for some of these novel pathways of 'endogenous' processing for class I-restricted epitope presentation is discussed. Some pathways are still hypothetical. The issue of alternative modes of 'endogenous' processing for class I-restricted antigen presentation is of theoretical and practical relevance. Immunologists are interested in the question from which source protein antigens are derived that are potentially accessible to specific recognition by different T cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A self-reactive class I-restricted T-cell response of H-2b mice to determinants of the V beta 8.2 domain of the T-cell receptor for antigen.

We studied the induction of a self-reactive cytotoxic T lymphocyte (CTL) response to determinants of the variable V beta 8.2 region of the beta-chain of the T-cell receptor (TCR) for antigen in C57BL/6 (H-2b) mice. A CTL response was elicited in vivo by TCR peptide vaccination, and detected in vitro using syngeneic transfectants expressing a rearranged V beta 8.2+ TCR beta-chain. The first series of experiments used a 15-mer peptide representing residues 68-82 of the V beta 8.2 domain and containing Kb and Db allele-specific motifs. Immunization with this peptide stimulated an autoreactive CTL response that cross-reacted with V beta 8.2 epitopes presented by transfectants endogenously processing a V beta 8.2+ TCR beta-chain. These transfectants expressed a construct derived from a murine, rearranged V beta 8.2/D beta 2/J beta 2.3/C beta 2 TCR beta-chain cDNA. The V beta 8.2+ T-cell subset of peptide-primed mice was not deleted but its proliferative response to stimulation by the V beta 8.2-specific monoclonal antibody (mAb) F23.2 was suppressed. In a second series of experiments we immunized mice with a 23-mer peptide representing residues 41-63 of the V beta 8.2 domain that does not contain putative, allele-specific H-2b class I-restricted motifs. This TCR peptide vaccination stimulated a CD8+ CTL response reacting against syngeneic, peptide-pulsed targets but not cross-reacting against transfectants processing/presenting epitopes of the beta-chain. V beta 8.2+ T cells of these peptide-primed mice were not anergized. These data demonstrate that vaccination with an immunogenic peptide representing a naturally processed epitope of the V beta 8.2 domain of the TCR beta-chain induces a self-reactive CD8+ CTL specific for this V beta 8.2 epitope; and anergizes (but does not delete) V beta 8.2+ T cells.

Amino Acid Sequence↗