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Biomedical subjects

R W Finberg

Publications and source records attributed to R W Finberg.

At least 91 records · Page 5Linked to original sources
PubMed1991

Murine T cell hybridoma-derived products regulate the growth of skeletal muscle myoblasts.

We have analyzed the effects of T cell products on the growth of murine myoblasts. Supernatants from some T cell hybridomas were shown to have either growth factor activity or growth inhibitory activity on two myoblast lines raised in our laboratory from two different strains of mice and also on the C2C12 myoblast line. The hybridoma-derived growth factor activity was shown not to require cofactors contained in serum as its effects could be demonstrated in assays done in serum-free media. Further studies on the effects of purified lymphokines on myoblasts using recombinant IL-2, IL-3, IL-4, IL-6, and GM-CSF showed these lymphokines not to have any growth stimulatory activity indicating that factor(s) other than the ones tested may be operative. Characterization by dialysis and column chromatography of hybridoma supernatants revealed the presence of a low-molecular-weight inhibitor and a higher-molecular-weight growth factor that was found in several hybridoma supernatants.

Animals↗
PubMed1991

The interaction of CD4 with HIV-1 gp120.

CD4 is an integral cell surface glycoprotein that is able to enhance T cell specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). Infection by HIV-1 is initiated by the binding of the envelope glycoprotein, gp120, to the first domain of CD4. The binding of CD4 to class II MHC is inhibited by gp120, one possible mechanism for immunosuppression in AIDS patients. In addition, the CD4/gp120 interaction may directly inhibit T cell function. Recently we have synthesized small molecules (CPFs) that specifically inhibit this interaction. CPFs bind to gp120 and prevent the binding of gp120 to CD4, and also inhibit the infectivity of HIV-1.

Animals↗
PubMed1991

Successful treatment of disseminated Fusarium infection after autologous bone marrow transplantation for acute myeloid leukemia.

Disseminated Fusarium is a rare but life-threatening infection of severely immunocompromised patients. A fatal outcome has been described in all reported cases of Fusarium infection occurring after bone marrow transplantation. We describe a patient who developed disseminated Fusarium infection with a secondary fungal endophthalmitis after an autologous bone marrow transplant for acute myeloid leukemia. This infection was successfully eradicated after neutrophil recovery by prolonged systemic administration of amphotericin B as well as aggressive local therapy including enucleation of the affected eye. The patient remains free of both leukemia and fungal disease more than 4 years after transplant.

Adult↗
PubMed1990

Prevention of HIV-1 infection and preservation of CD4 function by the binding of CPFs to gp120.

Infection by human immunodeficiency virus type-1 (HIV-1) is initiated when its envelope protein, gp120, binds to its receptor, the cell surface glycoprotein CD4. Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), blocked this binding. CPFs interacted with gp120 and did not interfere with the binding of CD4 to class II major histocompatibility complex molecules. One CPF isomer, CPF(DD), preserved CD4-dependent T cell function while inhibiting HIV-1 infection of H9 tumor cells and human T cells. Although the production of viral proteins in infected T cells is unaltered by CPF(DD), this compound prevents the spread of infection in an in vitro model system.

Animals↗
PubMed1990

Vaccination with a live retrovirus: the nature of the protective immune response.

We tested 3'-azido-3'-deoxythymidine (zidovudine) combined with interferon alpha as chemoprophylaxis after exposing mice to Rauscher murine leukemia virus. Therapy started 4 hr after inoculation and administered for 20 days prevented viremia and disease in all 234 mice tested. When the animals were rechallenged with live virus after cessation of therapy, 96% were resistant. The nature of this protective immune response was analyzed: Passive serotherapy of naive mice challenged subsequently with Rauscher murine leukemia virus was only protective at a high dose of immune serum. Immune, but not naive, T cells alone were fully protective against virus challenge. We conclude that vaccination with a live retrovirus that cannot replicate because of pharmacological blockade induces a T-cell response capable of protecting against a lethal retrovirus-induced disease.

Animals↗
PubMed1989

Human gamma delta+ T cells respond to mycobacterial heat-shock protein.

Most T cells recognize antigen through the T-cell antigen receptor (TCR)alpha beta-CD3 complex on the T-cell surface. A small percentage of T cells, however, do not express alpha beta but a second type of TCR complex designated gamma delta (ref. 2). Unlike alpha beta+ lymphocytes, gamma delta+ lymphocytes do not generally express CD4 or CD8 molecules, and the nature of antigen recognition by these cells is unknown. To study antigen recognition by gamma delta+ lymphocytes we raised a gamma delta+ alpha beta- -CD4-CD8- line from an individual immune to PPD (purified protein derivative). This line showed a specific proliferative response to PPD and to a recombinant mycobacterial heat-shock protein (HSP) of relative molecular mass 65,000 (65K). The gamma delta+ line was shown to exhibit a major response to HSP in the presence of autologous antigen-presenting cells (APCs). Minor responses occurred, however, with APCs matched for some HLA class I or II antigens, whereas no response occurred with HLA-mismatched APCs. These findings, therefore, document the requirement of HSP-reactive gamma delta+ lymphocytes for histocompatible APCs.

Antigen-Presenting Cells↗
PubMed1989

Intraperitoneal host cellular responses and in vivo killing of Bacteroides fragilis in a bacterial containment chamber.

A bacterial containment chamber was used to evaluate the peritoneal cellular response to Bacteroides fragilis during intraperitoneal challenge. This containment system was also used to determine the fate of bacteria within the peritoneal cavities of animals immunized, either actively or through adoptive transfer of cells or cell lysates, with the capsular polysaccharide of B. fragilis. This system demonstrated that the dominant cell types in the peritoneal cavities within 48 h of implantation of the containment chambers containing B. fragilis were neutrophils and macrophages. However, the early cellular response in immunized animals included an increase in the lymphocyte population within 4 h of challenge which was not detected in naive animals. In immunized animals, a later dramatic increase in the lymphocyte population at approximately 4 to 6 days following implantation of the containment chambers occurred. This increase in the lymphocyte population in immunized animals coincided with a decline in the viable bacterial counts within the chambers from 10(8) to 10(9) CFU/ml to less than 10(2) CFU/ml. A similar decline was not seen in naive animals challenged in the same manner. Killing of B. fragilis within containment chambers occurred when spleen cells, T cells, or lysates of T cells from actively immunized animals were passively transferred to naive recipient animals. It was shown that the factor responsible for bacterial killing was not antibody mediated, since bacteria contained within dialysis sacs with an exclusion of 50 kilodaltons were still killed in this model. Moreover, removal of T cells from adoptively transferred cell populations before transfer abrogated the decline in viable bacterial populations. The postulated mechanisms by which this bacterial killing occurred are discussed.

Animals↗
PubMed1987

Lymphokines induce specificity degradation in virus-induced cytolytic T-cell clones.

The target cell specificity of antiviral cytolytic T-lymphocyte (CTL) clones is influenced by in vitro tissue culture conditions. We have demonstrated that high concentrations of lymphokines such as recombinant interleukin-2 (rIL-2) induce killer T cells to lose virus specificity. Our experiments do not indicate that the cells become like natural killer (NK) cells. The loss of specificity is more general and can be reversed upon culture in more physiological concentrations of lymphokines. The implications of these observations for the pathogenesis of viral infection is discussed.

Animals↗
PubMed1987

The use of antiidiotypic antibodies as vaccines against infectious agents.

The development of the antibodies to the combining site of an antigen-binding antibody has been documented in humans as well as experimental animals. These antibodies have been shown in experimental models to have an important regulatory role in their ability to affect both B- and T-cell responses to antigen. Recently, with the development of technology for cloning T cells, it has been possible to produce monoclonal antibodies to the T-cell receptor proteins. These T-cell antiidiotypic antibodies have been shown to activate both B- and T-cell responses. For this reason, such reagents have the potential to be used as nonantigen-containing immunogens. Our work has demonstrated that such monoclonal anti-T-cell antiidiotypes are capable of stimulating immunity to lethal viral infections. The implications of the use of antiidiotypes against infectious organisms are discussed.

Animals↗
PubMed1986

Cellular control of abscess formation: role of T cells in the regulation of abscesses formed in response to Bacteroides fragilis.

Although abscesses are a major sequela of infection, little is known about which cellular events initiate and which prevent this pathologic response. These studies are the first to indicate a role for T cells in the important pathogenic process of abscess development and also in immunity to abscesses induced by Bacteroides fragilis. We have shown that T cells initiate the formation of abscesses in mice after i.p. challenge with B. fragilis. These T cells bear both Ly-1 and Ly-2 surface markers. Nude mice (which have been shown by others to have T cell or T cell precursors) are also able to form abscesses. Cyclophosphamide-treated mice (with depressed T cell function) were not capable of developing abscesses. Reconstitution with normal or nude mouse spleen cells restored this ability. However, reconstitution with anti-Thy-1.2-treated, anti-Ly-1, or anti-Ly-2-treated spleen cells (or a mixture of the two cell populations) failed to allow abscess formation after bacterial challenge. Immunity to abscesses caused by B. fragilis requires two T cells. The first Ly-1-2+ T cell has an IJ surface marker and has been shown to release a small m.w. soluble factor (ITF) that is antigen specific. Immunity to abscesses, however, depends on the interaction of ITF with a second Ly-1-2+ T cell, demonstrated in reconstitution experiments with nude mice. The data presented document a critical role for T cells in abscess induction and suggest the existence of a suppressor-like T cell circuit in immunity to abscesses.

Abscess↗
PubMed1986

Regulation of cytotoxic lymphocyte precursors. II. The effect of interleukin-2 and interferon-gamma on the apparent specificity of effector cells.

The influence of lymphokines on the frequency and specificity of antigen-induced cytolytic T cells was investigated. Removal of an acid-labile factor(s) from supernatants produced by concanavalin A (Con A)-stimulated rat splenocytes was shown to increase the specificity of cytolytic T-cell clones as determined by their ability to distinguish between antigen modified and unmodified target cells. The overall frequency of cytolytic T cell precursors (antigen specific as well as nonspecific) was reduced in the presence of acid-pretreated rat Con A supernatant as compared to untreated rat Con A supernatant. Neither the addition of interleukin 2 nor interferon-gamma could substitute for this acid-labile factor. These data indicate that an additional lymphokine(s) contributes to the in vitro activation of nonspecific killer cells.

Animals↗
PubMed1985

A soluble suppressor T cell factor protects against experimental intraabdominal abscesses.

This paper describes a suppressor T cell factor which protects mice against intraabdominal abscesses caused by Bacteroides fragilis. This soluble cell-free factor (ITF) is derived from splenic T cells from mice immunized with capsular polysaccharide (CP) of B. fragilis. Mice receiving ITF are protected from developing abscesses caused by B. fragilis to the same degree as animals receiving intact immune splenic T cells. The factor appears to be small in molecular size as protective activity is dialyzable through a 12,000-mol wt exclusion dialysis membrane and is present in fractions intermediate between the bed and void volumes of a P2 Biogel column. The protective effect of ITF is antigen-specific to B. fragilis alone. Mice given a complex inoculum of B. fragilis, enterococcus, and another anaerobe develop abscesses even after receiving column-purified ITF. The activity of ITF also is eliminated after adsorption with B. fragilis CP coupled to sheep erythrocytes but not with an unrelated CP coupled to sheep erythrocytes. ITF, therefore, appears to have a binding site for B. fragilis CP. ITF is heat-labile and loses efficacy after protease digestion, suggesting that the active material is a protein. These studies define a suppressor cell factor with activity in a model system resembling human disease and offer promise for increased understanding of the diversity of cell-mediated immune systems.

Abdomen↗
PubMed1985

Cell receptors for the mammalian reovirus. IV. Reovirus-specific cytolytic T cell lines that have idiotypic receptors recognize anti-idiotypic B cell hybridomas.

Cytotoxic T lymphocyte (Tc) cell lines specific for reovirus type 3 lysed an uninfected B cell hybridoma line, 87.92.6, that expresses and secretes an anti-idiotypic antibody that reacts with an anti-viral hemagglutinin monoclonal antibody, 9BG5. Monoclonal anti-idiotype 87.92.6 was shown by fluorescence analysis to specifically bind to reovirus Tc and to block reovirus-specific Tc from killing reovirus-infected target cells or the 87.92.6 hybridoma. An anti-LFA-1 monoclonal antibody, M17, interfered with Tc-mediated lysis of reovirus-infected targets and the 87.92.6 cells, indicating the similarity of cellular interactions mediated by LFA-1 structures when Tc bind to virally infected targets or 87.92.6 targets. Together with studies in which anti-H2 or monoclonal idiotypic antibodies were found to interfere with reovirus-specific Tc recognition of virally infected or 87.92.6 targets, these experiments indicate that some reovirus-specific Tc have conformations in their receptor that can be recognized by anti-idiotype.

Animals↗