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Biomedical subjects

L Steinman

Publications and source records attributed to L Steinman.

265 records · Page 15Linked to original sources
PubMed1978

Selective participation of immunoglobulin V region and major histocompatibility complex products in antigen binding by T cells.

Antigen-binding inhibition studies using microscopic autoradiography were performed on T or B cell-enriched lymphocyte populations. Antibodies specific for the "framework" of immunoglobulin heavy or light chain variable domains (VH or VL), or anti-H-2 and anti-Ia antisera were used. T cell subclasses were separated with anti-Lyt antisera and complement. It was found that antigen-binding T cells of different subclasses can be inhibited selectively with only one of the two anti-V region antibodies. Antigen binding to Lyt-1+ cells was inhibited by anti-VH, while Lyt-2+,3+ cells were inhibited by anti-VL specifically. Anti-Ia antisera inhibited unprimed Lyt-1+ antigen-binding cells, whereas anti-H-2K or anti-H-2D anti-sera inhibited unprimed Lyt-2+,3+ antigen-binding cells, and both classes of immune T antigen-binding cells.

Animals↗
PubMed1977

Physiological regulation of antigen binding to T cells: role of a soluble macrophage factor and of interferon.

A soluble product of macrophages (MF) and mouse viral interferon (IF) increase both major histocompatibility antigenic determinants and the number of antigen-binding cells in nonstimulated T cell-enriched mouse lymphocyte cultures. MF increases Ia and not H-2 antigens; IF increases H-2 but not Ia antigens. The increased antigen binding due to MF can be inhibited by anti-Ia but not by anti-H-2 sera, whereas IF-induced binding is sensitive to anti-H-2 but not to anti-Ia sera. The specificity of IF- or MF-induced binding of branched synthetic polypeptides by T cells is different from that of B cells and similar to the specificity of the Ir gene regulation. MF increases antigen binding only in Ir high-responder animals. The IF-induced antigen binding is not dependent on the Ir genotype. MF-reactive cells express the Ly-1 marker, and the IF-reactive antigen binders express the Ly-2 phenotype. It is suggested that MF and IF are physiological mediators of antigen binding by T cells.

Animals↗
PubMed1977

Unprimed spleen cell populations recognize macrophage-bound antigen with opposite net electric charge.

Previous studies have demonstrated an inverse charge relationship between the net electrical charge of antigen and the responding cells. In the present study we attempted to establish whether this phenomenon holds also for the primary recognition phase of cell-mediated immunity, when the involvement of the macrophage in presenting antigen is obligatory. Normal spleen cells were fractionated over negatively and positively charged columns. The fractionated cell populations, as well as the original cells, were sensitized in vitro on macrophage monolayers that were pulsed either with the basic encephalitogenic protein of myelin or with the acidic copolymer poly(Glu50,Tyr50). Cells eluted from glass bead columns(i.e., the more negative cells) could be sensitized only with the basic antigen, while cells eluted from poly(L-lysine)-glass bead columns (i.e., more positive cells) could be sensitized only to the acidic antigen. Thus, in delayed type hypersensitivity the inverse charge relationship prevails also for the primary immunological recognition of antigen bound to macrophages.

Animals↗
PubMed1971

The uptake of ( - 3 H) aminobutyric acid in the goldfish retina.

After goldfish retinas had been incubated for 1 hr with [gamma-(3)H]aminobutyric acid, we found by autoradiography that the label was localized to a few restricted types of retinal cells. In particular, external and internal horizontal cells from light-stimulated retinas were more heavily labeled than corresponding cells from retinas kept in darkness. Some other cells and tissues in the retina also incorporated the labeled acid. Light stimulation, however, did not cause a pronounced change in the amount of label associated with these cells. Among these were some heavily labeled cells on the vitreal side of the inner nuclear layer, and scattered grains associated with the ganglion cell and optic nerve layers. Electrophoresis of retinal extracts after incubation with the labeled acid also showed that light-stimulated retinas contained about 40-100% more radioactivity than retinas kept in darkness, and that 90% of this activity remained as [gamma-(3)H]aminobutyric acid. The role of the acid in the retina is not known; it is not clear if horizontal cells normally synthesize or store it. The stimulation-dependent accumulation of the labeled acid into horizontal cells suggests that it plays a functional role in these cells.

Aminobutyrates↗
PubMedDate not supplied

Competitive PCR quantification of CD4, CD8, ICAM-1, VCAM-1, and MHC class II mRNA in the central nervous system during development and resolution of experimental allergic encephalomyelitis.

We used competitive polymerase chain reaction to quantify messenger RNA for the lymphocyte antigens CD4 and CD8, the adhesion molecules ICAM-1 and VCAM-1, and the MHC class II I-A molecule in the spinal cords of SJL/J mice at multiple times during the development and resolution of experimental allergic encephalomyelitis (EAE). CD4 and CD8 were not quantifiable at baseline, became detectable at 5 days after immunization, and increased steadily to a peak during clinical disease. I-A increased after CD4 and CD8, but before onset of disease. ICAM-1 and VCAM-1 did not increase until after onset of clinical disease. CD4, CD8, and I-A remained elevated long after recovery from disease. These results suggest that infiltration of CD4 and CD8 cells into the spinal cord and subsequent upregulation of I-A mRNA play an important role in the development of EAE, but reversal of these processes is not necessary for recovery. Upregulation of ICAM-1 and VCAM-1 mRNA does not appear to be important for development of disease.

Animals↗
PubMedDate not supplied

T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination.

Experimental allergic encephalomyelitis (EAE) serves as a model for autoimmune diseases mediated by T lymphocytes. Following sensitization to rat, mouse or guinea pig myelin basic protein (MBP) in complete Freund's adjuvant, inbred mouse strains PL/J (H-2u), SJL/J (H-2s) and (PL/J X SJL/J)F1((PLSJ)F1) develop EAE. Whereas sensitization to the N-terminal 37 amino-acid peptide of rat or guinea pig MBP [MBP(1-37)] induces EAE in PL/J mice, immunization to the C-terminal peptide (89-169) leads to EAE in SJL/J mice. The immune response to MBP in (PLSJ)F1 mice is not co-dominant; sensitization to the N-terminal peptide induces EAE, while sensitization to the C-terminal peptide does not. We have generated MBP-specific T-cell clones restricted to class II (Ia) antigens of the major histocompatibility complex (MHC) from PL/J and (PLSJ)F1 mice following sensitization to rat MBP. Two such I-Au-restricted T-cell clones that proliferate in response to the encephalitogenic N-terminal MBP peptide and recognize a shared determinant with mouse (self) MBP cause paralysis in 100% of (PLSJ)F1 mice tested. Paralysis is induced even when recipients are injected with as few as 1 X 10(5) cloned T cells. Relapsing paralysis followed in two-thirds of the recipients after recovery from acute paralysis, whereas one-third developed chronic persistent paralysis, a form of EAE not usually seen. Histopathology revealed intense perivascular inflammation, demyelination and remyelination within the central nervous system of paralysed mice. The experimental disease induced with these clones shares important features with human demyelinating diseases such as multiple sclerosis. This is the first demonstration that T-cell clones that respond to a defined self-antigen can induce clinical and histological autoimmune disease.

Animals↗
PubMedDate not supplied

T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis.

Chronic relapsing paralysis and demyelination within the central nervous system (CNS), features associated with the human disease multiple sclerosis (MS), develop in mice after injection of murine T-cell clones specific for the autoantigen myelin basic protein (MBP). We examined the fine specificity of three independently derived encephalitogenic T-cell clones using synthetic polypeptides derived from portions of the N-terminal sequence of MBP. These clones appear functionally identical; they all respond to an epitope in the N-terminal nine amino acid residues in association with the same class II (I-A) molecules of the major histocompatibility complex (MHC). Both the N-terminal acetyl moiety and the first residue (Ala) are necessary for recognition. Only N-terminal MBP peptides recognized by these clones were found to cause encephalomyelitis (EAE) in vivo. These results show that the N-terminal MBP-specific T lymphocytes that mediate autoimmune encephalomyelitis are a small population with a limited repertoire; they all recognise the same combination of MHC and target.

Animals↗
PubMedDate not supplied

Molecular approaches toward a therapy for multiple sclerosis.

Treatment of experimental allergic encephalomyelitis with monoclonal antibodies to products of immune response genes and to surface markers on T cells was reviewed. Both anti Ia therapy and anti T4 therapy can reverse ongoing paralysis, and block subsequent relapses. The appearance of T4 cells and Ia antigens in relapse was demonstrated. The prospects for human therapy with chimeric human-mouse immunoglobulins and isotypic variants was discussed, with particular attention to the immunotherapy of multiple sclerosis.

Animals↗
PubMedDate not supplied

Coccidioidal antigen reactive CD4+ T-lymphocytes in the cerebrospinal fluid in coccidioides immitis meningitis.

CSF lymphocytes from patients with Coccidioides immitis meningitis exhibited a significant antigen-specific response to in vitro stimulation with C. immitis antigens. In some patients, lesser responses to control antigens (Candida and PPD) were also detected. Antigen-specific responses by CSF lymphocytes were seen early in the course of this disease as well as several years after patients had entered remission. When compared to CSF cells, the response of autologous peripheral blood mononuclear cells was similar but of a much smaller magnitude and at times undetectable. Fluorescence activated cell sorting revealed an increased percentage of CD3+ (T-cells), CD4+ (helper/inducer) and CD3+/HLA-DR+ (activated T-cell) cells in the CSF of C. immitis meningitis patients compared to their blood. Most of the antigen-specific proliferative response resided in the CD4+ lymphocyte subset. CSF T-cell proliferation assays may have a role in the diagnosis of C. immitis meningitis.

Adolescent↗