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Biomedical subjects

R W Hoffman

Publications and source records attributed to R W Hoffman.

49 records · Page 3Linked to original sources
PubMed1986

Specific targeting of human peripheral blood T cells by heteroaggregates containing anti-T3 crosslinked to anti-target cell antibodies.

Antibody heteroaggregates have been used to render human peripheral blood T cells lytic for specified targets. The heteroaggregates contain anti-T3 covalently linked to antibodies against nominal target cell antigens. Such heteroaggregates bind target cells directly to T3 molecules on effector cells and trigger target cell lysis. Freshly prepared human PBL, when coated with anti-T3-containing heteroaggregates, are lytic without further stimulation, although brief exposure to crude lymphokine-containing supernatants or recombinant IL-2, but not recombinant IFN-gamma, enhances the activity. The effector cells are T8+, and when fully stimulated, their lytic activity approaches that of some cloned CTL. When T cells are treated with heteroaggregate, washed, and incubated at 37 degrees C in medium not containing heteroaggregate, they retain activity for at least 24 h. The results of this study suggest a strategy in which heteroaggregate-coated T cells could be used in vivo to mount a lytic response against pathogenic cells such as tumor cells or virus-infected cells.

Antibodies↗
PubMed1986

HLA-DP antigens in patients with pauciarticular juvenile rheumatoid arthritis.

The distribution of the recently described HLA-DP antigens was examined in a population of patients with pauciarticular juvenile rheumatoid arthritis and iridocyclitis, in an attempt to further characterize the immunogenetically determined susceptibility to this disease. There was a significantly increased frequency of the HLA-DPw2 antigen in the patients compared with the controls (67% versus 34%; odds ratio 3.9, P = 0.003 by Fisher's exact test). Population studies and family studies showed that this association with HLA-DPw2 was not secondary to linkage disequilibrium with the previously defined HLA-D region markers of disease (HLA-DR5 and HLA-DRw8) in these patients. These data raise the possibility that susceptibility to this form of juvenile rheumatoid arthritis may be regulated by more than one HLA-linked gene.

Arthritis, Juvenile↗
PubMed1985

Anti-T3 antibody both activates and inhibits the cytotoxic activity of human T cell clones.

The present report outlines results using several approaches to investigate the effects of antibodies against cell surface molecules on human cytotoxic T lymphocyte (CTL) recognition. First, when interactions between CTL and targets are perturbed by antibody immobilized on the surface of the incubation vessel, anti-T3 antibody was unique in its ability to inhibit at least 10 times more efficiently than when present in solution. Second, anti-T3 antibody at sufficiently high concentrations inhibits lectin-dependent cellular cytotoxicity as well as allospecific cytotoxicity. Third, murine hybridomas expressing anti-T3 antibody induce their own lysis by human CTL clones; but hybridomas bearing antibodies of other specificities are not lysed in a similar manner. We have exploited this anti-T3 triggered lysis of the OKT3 hybridoma as a model system in which to study T cell recognition. Such lysis is susceptible to inhibition not only by anti-T3 but also by anti-LFA-1 antibody; however, conjugate formation between the anti-T3 hybridoma and CTL is not easily inhibited by anti-LFA-1. These data, which are discussed in the context of results from other laboratories, are consistent with a model in which CTL triggering can be induced by interaction of the antigen specific receptor (Ti) with its physiologic ligand, antigen plus MHC, or interaction of the T3 complex with a surrogate ligand, anti-T3/anti-Ti. However, they raise questions regarding the role which LFA-1 plays in CTL recognition.

Animals↗
PubMed1984

Sjögren's syndrome in MRL/l and MRL/n mice.

Six autoimmune murine models (MRL/l, MRL/n, NZB, NZB/NZW, PN, C57BL/6J-lpr/lpr) were compared with normal control C57BL/6J and DBA/2 mice to determine if spontaneous autoimmune disease was associated with evidence of Sjögren's syndrome. Schirmer tests documented dry eyes in NZB/NZW and PN mice; other autoimmune strains and controls had normal tear formation. All autoimmune mice had conjunctivitis, but this abnormality was most severe in the PN strain. Ninety-eight percent of MRL/l and MRL/n mice had mononuclear cell infiltrates in lacrimal glands, and salivary glands were involved to a lesser degree. New Zealand mice and PN mice had smaller gland lesions. The extensive gland destruction in MRL/l and MRL/n mice suggested that these substrains merit further studies as animal models of Sjögren's syndrome.

Animals↗
PubMed1983

Band keratopathy in MRL/l and MRL/n mice.

To define ocular abnormalities in mice with autoimmune disease, we performed biomicroscopic examinations and examined ocular tissue in MRL/l, MRL/n, NZB, NZB/NZW, and Palmerston North mice. Results were compared with MRL/Mp--lpr/lpr, C57BL/6J--lpr/lpr, and normal control strains. Eighty-seven percent of MRL/l and MRL/n mice had typical band keratopathy; this was confirmed by histologic examination. Posterior uveitis was found in 35% of adult MRL/l mice. MRL substrains are potentially important models of ocular disease.

Animals↗
PubMed1982

Intrathoracic and multiple abdominal pheochromocytomas in von Hippel-Lindau disease.

A patient had von Hippel-Lindau disease, a functional intrathoracic paraganglioma (pheochromocytoma), bilateral adrenal pheochromocytomas, and a para-adrenal pheochromocytoma. Seven other members of the patient's family had features of von Hippel-Lindau disease and one, a cousin, had medullary carcinoma of the thyroid. This is the first report of a pheochromocytoma arising outside the abdomen in von Hippel-Lindau disease and the 25th report of intrathoracic pheochromocytoma in the literature. The association between von Hippel-Lindau disease and pheochromocytoma is reviewed.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody.

The specificity of cytotoxic T lymphocytes (Tc) cells is conferred by an antigen-specific receptor, Ti, which in humans is physically associated with an invariant cell-surface glycoprotein, T3. Monoclonal antibodies specific for either T3 and Ti are able to elicit a variety of T-cell responses such as lymphokine production, mitogenesis and cytotoxicity. For example, human Tc cells lyse anti-T3-expressing hybridoma cells, but not cells of other specificity, presumably because anti-T3 on the hybridoma cells binds to T3 on the Tc cells and triggers lysis. Here, we have adapted approaches used in a different cytotoxic effector system, antibody-dependent cellular cytotoxicity (ADCC), to alter the specificity of Tc cell. Studies of ADCC showed that heteroaggregates containing anti-Fc receptor (Fc gamma R) antibody cross-linked to a second antibody bind to Fc gamma R on ADCC effectors and cause them to kill target cells bearing antigen recognized by the second antibody. The present studies use anti-T3-containing heteroaggregates to re-target human Tc cells to cells for which we have appropriate antibodies, including xenogeneic tumour cells and chicken erythrocytes. These results extend previous observations on the role of T3 in triggering cytotoxicity and suggest that effector cell re-targeting could be used for in vivo treatment of neoplasms and other pathogens that express distinctive surface antigens.

Animals↗
PubMedDate not supplied

Structural analysis of TCRalpha and beta chains from human T-Cell clones specific for small nuclear ribonucleoprotein polypeptides Sm-D, Sm-B and U1-70 kDa: TCR complementarity determining region 3 usage appears highly conserved.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are systemic autoimmune diseases that are characterized by the presence of autoantibodies reactive with U small nuclear RNP (snRNP) autoantigens. Both B and T cells are important in the pathogenesis of the disease, and T- and B-cell immunity against snRNP polypeptides have been shown to be linked in vivo. Currently, several alternative hypotheses for the pathogenesis of these diseases have been proposed. These include loss of tolerance, modified self-antigens, molecular mimicry and nondirected immune activation. To help distinguish between the various models of disease pathogenesis, we have characterized the T-cell receptor (TCR) CDR3 from a large panel of well-characterized human T-cell clones and lines specific for individual snRNP polypeptides. The results presented here reveal highly restricted TCR usage across patients by the snRNP-reactive T cells based on the deduced amino acid sequence of the CDR3 loop. These data support the hypothesis that T-cell responses against self antigens in SLE and MCTD are antigen driven and that there are a limited number of T-cell epitopes present on the snRNP autoantigens.

Amino Acid Sequence↗