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Biomedical subjects

R Finberg

Publications and source records attributed to R Finberg.

At least 55 records · Page 3Linked to original sources
PubMed1982

I-J-restricted interactions in the generation of azobenzenearsonate-specific suppressor T cells.

The genetic restrictions of the activation of third-order suppressor cells (Ts3) were studied in mice, using two different types of anti-azobenzenearsonate (ABA)-immune responses, namely delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) generation. Ts2 cells were induced in several different strains of mice by injecting monoclonal T hybridoma molecules or first-order suppressor factors (TsF1) originating in A/J (H-2a, Igh-1e) mice and then testing the TsF2 molecules derived from these Ts2 in A/J and A.By (H-2b, Igh-1e) or (A/J X A.By)F1 (H-2a/b, Igh-1e) and (C57Bl/6 X A/J)F1 (H-2b/a, Igh-1e) mice. It was shown that the activity of TsF2 was restricted to the I-J of the strain in which Ts2 was induced. By genetic analysis, restriction was shown to be due to the requirement of H-2 identity between ABA-coupled cells used for Ts3 activation and the strain of the TsF2 origin. Moreover, by using H-2-congenic ABA-coupled cells, we were also able to precisely map and demonstrate that ABA-coupled cells I-J identical to TsF2 induced in various strains were necessary for effective suppression to occur. This selective activation of Ts3 suggested the existence of I-J-related antigen presentation for suppression as the counterpart of I-A or I-A-I-E-restricted antigen presentation for positive immune responses.

Animals↗
PubMed1982

Two distinct mechanisms regulate the in vivo generation of cytotoxic T cells.

Treatment of responder cells with monoclonal anti-Ly-1,2 antibodies plus complement in vitro completely eliminated their ability to generate azobenzenearsonate (ABA)-specific cytolytic T lymphocytes (CTL). However, addition of the concanavalin A-stimulated supernatants of rat spleen cells (Con A-Sup) can fully reconstitute the response. Therefore, Lyt-1,2-bearing T cells are required for the generation of ABA-specific CTL, and such requirement can be replaced by factors present in the Con A- sup. Suppressor T cells (Ts), when adoptively transferred into naive recipients, will inhibit the in vivo priming of CTL. This inhibition can also be reversed by in vitro addition of Con A-Sup. furthermore, mice serving as donors of Ts also show profound unresponsiveness when primed and restimulated in vitro. In contrast to the Ts-mediated inhibition, in vitro addition of Con A-Sup was unable to abolish the unresponsiveness observed in these cultures. Thus, we identified two unresponsive states in a hapten-specific killing system that differ in their ability to be reconstituted by Con A-Sup.

Animals↗
PubMed1982

CT hybridomas: tumor cells capable of lysing virally infected target cells.

By fusing primed murine lymphocytes with a syngeneic T cell lymphoma, we have been able to select for H-2-restricted, virus-specific cytotoxic T cell hybridomas (CTH). These T cell hybrids, which replicate in ordinary tissue culture medium or in ascites, are capable of lysing virally infected target cells, and their activity is facilitated by the presence of lectins in the assay medium. Unlike cells mediating lectin nonspecific lysis, these hybridomas are H-2 restricted and specific for single viral proteins. The ability to maintain these cells in culture for over 18 mo and to pass them in vivo without loss of activity or specificity indicates that they will provide sufficient material for the analysis of surface proteins and genetic information required for the recognition and lysis of virally infected cells by killer T cells.

Animals↗
PubMed1982

Host immune response to reovirus: CTL recognize the major neutralization domain of the viral hemagglutinin.

Previous studies have demonstrated the importance of the hemagglutinin (HA) of reovirus in determining virus-specific immune responses. In this study, we have used anti-HA monoclonal antibodies and reoviruses with antigenically altered HA proteins to further analyze the CTL response against the HA. We showed that reovirus-specific CTL primarily recognize one distinct antigenic domain on the HA. These results emphasize the fine specificity of the T cell receptor that recognizes viral determinants. The CTL response is directed against the region of the HA that is also responsible for neurotropism and binding to neutralizing antibody.

Animals↗
PubMed1982

An adherent cell lyses virus-infected targets: characterization, activation, and fine specificity of the cytotoxic cell.

We have previously reported that mice with defective T lymphocyte function clear a primary reovirus type 1 infection in a normal fashion. The present studies were initiated to determine what cells may play a role in the clearance of this primary infection. We show that macrophages from unprimed mice are capable of lysing reovirus type 1-infected target cells in the absence of specific antibody. Macrophages from nu/nu mice have higher levels of this lytic activity than macrophages from nu/+ and normal mice. In addition, PEC from endotoxin nonresponsive C3H/HeJ mice have virtually no anti-viral lytic activity, while PEC from C3H/FeJ mice have high levels of such activity. Incubation of PEC from C3H/HeJ mice overnight in Con A supernatants restores this lytic activity. PEC are capable of lysing reovirus type 1-infected target cells but not those infected with type 3 reovirus. Using intertypic recombinant viruses, we show this striking target cell specificity to be a property of the sigma 1 protein, the viral hemagglutinin.

Animals↗
PubMed1982

Biologic activity of an idiotype-bearing suppressor T cell factor produced by a long-term T cell hybridoma.

Biologic activities and immunochemical characteristics of an azobenzenearsonate- (ABA)specific suppressor T cell factor produced by a longterm T cell hybridoma, F12, were studied. In vivo administration of F12 culture supernatant resulted in the suppression of ABA-specific delayed-type hypersensitivity (DTH) responses and the inhibition of priming for ABA-specific cytotoxic T lymphocyte responses. Moreover, F12 induced a second set of suppressor cells that act in the efferent phase of DTH. The active material in the F12 culture supernatant expressed major cross-reactive idiotypic (CRI) determinants of anti-ABA antibodies of A/J mice and I-J subregion-coded specificities but not express determinants of immunoglobulin constant regions. These results demonstrated that F12 is a functioning hybrid cell line of the first-order suppressor T cell subset.

Animals↗
PubMed1981

Intestinal M cells: a pathway for entry of reovirus into the host.

Thirty minutes after inoculation of reovirus type 1 into the intestinal lumen of the mouse, viruses were found adhering to the surface of intestinal M cells but not other epithelial cells. Within 1 hour, viruses were seen in the M cell cytoplasm and were associated with mononuclear cells in the intercellular space adjacent to the M cell. These findings suggest that M cells are the site where reovirus penetrates the intestinal epithelium.

Animals↗
PubMed1981

Type-specific reovirus antiserum blocks the cytotoxic T-cell-target cell interaction: evidence for the association of the viral hemagglutinin of a nonenveloped virus with the cell surface.

It has previously been demonstrated that spleen cells from mice immunized with reovirus type 1 or 3 generate virus-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation. Such cytotoxic T cells lyse H-2 identical targets that are infected with the appropriate reovirus type. Viral recombinants were used to demonstrate that the S1 gene is the predominant viral gene determining the specificity of the CTL. Reoviruses are nonenveloped, non-membrane-maturing viruses; therefore, it was important to determine whether viral products were being recognized by CTL on the surface of target cells. Antiserum blocking was utilized to investigate this issue. Using viral recombinants and antisera to reoviruses types 1 and 3, we were able to demonstrate that the major viral antigen recognized by the CTL on the target cell surface is the sigma 1 polypeptide encoded by the S1 genome segment. Thus, viral antigens on the target cell membrane seem to be important in the CTL response to a nonenveloped, non-membrane-maturing virus.

Animals↗
PubMed1981

T lymphocyte immunity to reovirus: cellular requirements for generation and role in clearance of primary infections.

The cellular requirements for the development of an immune response to reovirus type 1 and the role of such a response in the clearance of a primary infection with that virus were explored. An Ia-bearing antigen-presenting cell requirement is demonstrated for the in vitro generation of secondary anti-reovirus cytolytic T lymphocytes (CTL). It is then shown that mice whose spleens are depleted of Ia-bearing adherent cells by exposure in vivo to ultraviolet (UV) radiation exhibit depressed priming for reovirus-specific T lymphocyte function-CTL generation, delayed-type hypersensitivity reactivity, and T cell proliferative responsiveness. These UV-irradiated mice clear primary systemic reovirus infections as readily as normal mice. Further, athymic 'nude' mice show no defect in their ability to clear a reovirus infection. The implications of these findings for our understanding of the role of virus-specific T cell function in the clearance of systemic viral infections are discussed.

Animals↗
PubMed1980

The origins of alloreactivity: differentiation of prekiller cells to viral infection results in alloreactive cytolytic T lymphocytes.

Mice maintained in our animal colony become primed to Sendai virus. This "environmental" priming is reflected in a shift in prekiller activity from the Ly 123 to Ly 23 T cell set and in increased virus-specific cytolytic activity. This transition is accompanied by the development of cytolytic activity against allogeneic targets (not expressing Sendai antigens). These findings are consistent with the view that continued stimulation of Ly 123 cells by autologous MHC antigens, associated with foreign antigens such as a virus, generate Ly 23 prekiller cells that respond to alloantigens as well as autologous cells infected with the relevant virus.

Animals↗
PubMed1979

Generation of cytolytic T lymphocytes after reovirus infection: role of S1 gene.

Cytotoxic T lymphocytes (CTLs) can be generated if spleen cells from reovirus-infected mice are stimulated in vitro with syngeneic reovirus-infected cells. These cytolytic effector cells demonstrate: (i) serotype specificity (i.e., maximal cytolytic activity is observed on target cells infected with the serotype used to induce the CTLs) and (ii) H-2 restriction. The SI gene was shown to be the predominant viral gene determining the specificity of the cytotoxic T cells. This genome segment has previously been demonstrated to encode the viral hemagglutinin and determines reovirus cell tropism in the nervous system.

Animals↗
PubMed1979

The cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells. I. Evidence for antigen-specific helper T cells.

Mice were primed subcutaneously with trinitrophenyl (TNP)-modified syngeneic spleen cells. Seven days later, spleen cells from these in vivo primed mice, or spleen cells from naive mice, were co-cultured with TNP-modified syngeneic cells. Spleen cells from the in vivo primed mice demonstrated augmented cytolytic T lymphocyte (CTL) activity. The spleens of these in vivo primed mice contained a population of radioresistant, antigen-specific, helper T cells. Specifically, spleen cells from these mice, after x-irradiation, were able to augment the in vitro CTL response of normal spleen cells to TNP-modified syngeneic cells.

Animals↗
PubMed1979

The cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells. II. Evidence for antigen-specific suppressor T cells.

The subcutaneous administration of trinitrophenyl (TNP)-coupled syngeneic cells 7 days before co-culture with TNP-coupled syngeneic stimulator cells results in increased cytolytic activity. This augmented cytotoxic response has been shown to be dependent, at least partially, on radioresistant "helper" T cells. In this paper we have demonstrated that TNBS-generated suppressor T cells that are capable of suppressing contact sensitivity can specifically suppress the augmented response seen after subcutaneous priming. The i.v. administration of TNP-coupled cells results in priming of the recipient; however, if cells from these animals are transferred to a second recipient, there is evidence of suppressor activity. Thus, the cytotoxic T lymphocyte response is controlled by the same type of complex interactions previously demonstrated for humoral and delayed-type hypersensitivity responses.

Animals↗
PubMed1978

The induction of virus-specific cytotoxic T lymphocytes with solubilized viral and membrane proteins.

Reconstituted membranes were prepared from detergent solubilized P815 (H-2d) tumor cell membranes and solubilized Sendai virus protein. These reconstituted membranes stimulated a virus-specific H-2-restricted secondary CTL response. Stimulating activity was dependent upon the presence of both viral and P815 protein in the same membrane and was restricted to the H-2 specificity present in the reconstituted membrane. Liposomes prepared from solubilized Sendai virus proteins and partially purified H-2 alloantigen also had activity for CTL induction. The results demonstrate the feasibility of using detergent solubilized membrane proteins to study antigen recognition by virus-specific, H-2 restricted cytolytic T lymphocytes.

Animals↗
PubMed1978

The biologic significance of alloreactivity. The ontogeny of T-cell sets specific for alloantigens or modified self antigens.

We have analyzed the cellular basis of T-cell reactivity against lymphocytes expressing major histocompatibility complex (MHC) products that are foreign by virtue of polymorphism (alloantigens) or because of modification by chemicals or viruses. We find that early in ontogeny, prekiller activity against both trinitrophenyl (TNP)-coupled autologous MHC products and allogeneic MHC products resides in the same (Ly123(+)) T-cell pool; later in ontogeny alloreactivity is invested in Ly23 cells which, when activated, lyse TNP-coupled autologous cells as well as appropriate allogeneic target cells. We demonstrate that stimulation of Ly123(+) T cells in vitro by autologous cells coated with chemically-inactivated Sendai virus results in the formation of Ly23(+) cytolytic T lymphocytes (CTL) that specifically lyse both virus modified autologous target cells and unmodified allogeneic target cells. These results suggest the following model to account for the presence of large numbers of alloreactive T-cell clones in adult animals: continuous stimulation of Ly123 cells by autologous MHC antigens associated with foreign materials such as a virus results in the formation of Ly23 memory progeny carrying receptors that recognize MHC products that are foreign due to genetic polymorphism (alloantigens). In general, these studies indicate that alloaggression (as manifest by Ly23 cells in the CTL response) reflects a high degree of cross stimulation between physiologically relevant antigens, e.g., viral determinants associated with self MHC products, and biologically irrelevant allelic variants of the MHC.

Animals↗
PubMed1978

Biological significance of alloreactivity: T cells stimulated by Sendai virus-coated syngeneic cells specifically lyse allogeneic target cells.

In vitro stimulation of spleen cells from mice immune to Sendai virus results in the generation of effector cells that lyse unmodified allogeneic target cells in addition to syngeneic cells modified by virus. These cells are immunologically specific because their lysis may be blocked by cold targets syngeneic to either the stimulator or the responder. These results support our proposal that the development of alloreactivity can be explained by the crossreactivity between modified self major histocompatibility complex antigens and alloantigens. We propose that exposure to autologous major histocompatibility complex antigens modified by foreign antigens in our environment results in the expansion of the pool of T cells that will respond to alloantigens sharing crossreactive determinants.

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