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Biomedical subjects

H Wekerle

Publications and source records attributed to H Wekerle.

222 records · Page 13Linked to original sources
PubMed1972

Fractionation of antigen reactive cells on a cellular immunoadsorbent: factors determining recognition of antigens by T-lymphocytes.

Monolayers of mouse fibroblasts were used as cellular immunoadsorbents to separate rat lymphocytes that recognize specific mouse histocompatibility antigens. Normal lymphocytes were incubated on fibroblasts of strain C3H/eb, and nonadherent cells were separated from adherent cells, then transferred for sensitization onto fresh monolayers of C3H. When tested on (51)Cr-labeled target monolayers the nonadherent cells manifested significantly lower cytotoxicity than the adherent cells. However, the nonadherent cells could be sensitized against mouse fibroblasts of an unrelated H-2 phenotype (strain Balb/c). The immune specificity of the adherence was further demonstrated by a stepwise adsorption, which resulted in complete loss of the capacity to acquire specific lytic activity towards C3H antigens. Lymphocytes recognizing strain-specific antigens of the mouse were separated at 37 degrees (not at 0 degrees or 4 degrees ); separation was inhibited after treatment with dinitrophenol, sodium azide, or trypsin. Prior treatment with neuraminidase rendered the lymphocytes suceptible to separation at 0 degrees .

Adsorption↗
PubMedDate not supplied

The effect of silyl substituted methotrexate in the treatment of experimental allergic encephalomyelitis in rats mediated by T-line cells.

The effect of methotrexate and of silyl-methotrexate were compared in the treatment of experimental allergic encephalomyelitis (EAE) mediated by T-line lymphocytes. It was demonstrated that, during the first three days after cell transfer, no difference between methotrexate and its silyl derivative could be seen. At a time when the cytotoxic lymphoblasts must have penetrated the blood brain barrier, only silyl methotrexate was able to prevent severe paralysis and death of the animals. It is suggested that the effect of N,N,O,O-Tetrakis (t-butyldimethylsilyl)-methotrexate, (N-4-N-(2,3-bis-t-butyldimethylsilyl-amino-6-pteridinyl-methyl)- methylamino-benzoyl-glutamic acid-bis-(t-butyldimethylsilyl)-ester), depends on the increased lipid solubility and permeability of the blood brain barrier of silylated drugs.

Animals↗
PubMedDate not supplied

Astrocytes present myelin basic protein to encephalitogenic T-cell lines.

Astrocyte proliferation and perivascular lymphocyte infiltration are conspicuous among the cellular changes in the active brain lesions of multiple sclerosis patients. Recent observations have indicated that most of the perivascular lymphocytes are T cells which may be actively involved in the generation of the brain lesions. Much less is known about the significance of the proliferative astrocytes, although the fact that they produce an interleukin-1 (IL-1)-like factor that enhances the release of interleukin-2 by T lymphocytes, may provide a clue. We show here that rat astrocytes are able to present antigen to T lymphocytes in a specific manner which is restricted by the major histocompatibility complex (MHC) and that they can in particular activate myelin basic protein (BP)-specific, encephalitogenic T-cell lines. Only on such interaction do astrocytes express Ia antigens in easily detectable amounts. Antigen presentation by astrocytes may have a central role in the generation of immune responses in the brain.

Animals↗
PubMedDate not supplied

Ia-restricted encephalitogenic T lymphocytes mediating EAE lyse autoantigen-presenting astrocytes.

T lymphocytes specific for myelin basic protein (MBP) are responsible for the cellular events leading to autoimmune disease within the central (CNS) and peripheral (PNS) nervous systems. Both in actively induced and T-cell transfer versions of experimental autoimmune encephalomyelitis (EAE) and neuritis (EAN), the autoaggressive T cells are activated outside the nervous system and reach their target tissue via the blood circulation. The target specificity of the autoaggressive T cells is impressive; T-cell lines specific for MBP predominantly home to and affect the white matter of the CNS whereas T cells specific for PNS myelin protein P2 exclusively infiltrate peripheral nerves. Having penetrated the tight blood tissue barriers, the lymphocytes seem to interact with local cells expressing the relevant autoantigen in an immunogenic form. Although the exact mechanism of target finding and destruction is unknown, studies from our laboratory have shown that astrocytes, a main component of the normal CNS glia, can actively present antigen to specific T cells. This observation suggests that astrocytes are involved in natural immune reactivity within the CNS, and that they may be involved in pathological aberrations, such as in the development of autoimmune lesions. Having studied astrocyte/T-cell interactions in more detail, we discovered that encephalitogenic T-cell lines recognizing MBP on astrocytes will subsequently proceed to kill the presenting cells. Here we report that astrocyte killing follows the rules governing 'classical' T-cell-mediated cytolysis; it is antigen-specific, restricted by antigens of the major histocompatibility complex (MHC) and apparently contact-dependent. Our data suggest that the nature of the recognized antigenic epitope determines whether or not antigen recognition is followed by killing; moreover, killing of antigen-presenting astrocytes seems to be correlated with the capacity to transfer encephalomyelitis to normal syngeneic rats.

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