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F Plata

Publications and source records attributed to F Plata.

At least 37 records · Page 2Linked to original sources
PubMed1988

Evidence for a cytotoxic T-lymphocyte alveolitis in human immunodeficiency virus-infected patients.

A T8 lymphocyte alveolitis occurs in HIV-positive patients, even in the absence of any lung infections or tumors. Using the monoclonal antibody (MAb) D44, the CD8+ T cells can be further subdivided into two functional subsets of cytotoxic T lymphocytes (CTL; CD8+, D44+) and suppressor T cells (CD8+, D44-). A dual fluorescence analysis of alveolar and peripheral lymphocytes has been used in HIV-positive patients without lung infections or tumors to reveal a dramatic increase in alveolar T8 lymphocytes (83%), compared to peripheral values (52%), which was mainly composed (89%) of CD8+ D44+ CTLs. Functional studies confirmed the cytolytic activity of these phenotypically defined alveolar CTLs on autologous alveolar macrophages used as target cells, excluding a natural killer-like activity. An immuno-enzyme analysis concomitantly revealed the co-expression of the p18 HIV antigen and the CD4 molecule on the autologous alveolar macrophages. These data suggest that CTL alveolitis occurs during HIV infection and is directed against HIV-infected alveolar macrophages which are presumably the targets of the locally recruited lung CTLs.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Fine mapping of epitopes by intradomain Kd/Dd recombinants.

11 intradomain recombinants between H-2Kd and H-2Dd were produced using an original technique based on in vivo recombination in Escherichia coli. After transfection into mouse L cells, all these recombinants were expressed at high levels on the cell surface. The specificities of 77 mAbs were examined on these cell lines. mAbs could be organized in 12 groups. In each group, a small number of amino acids participating in the recognized epitope(s) were identified. In a few instances, noncontinuous epitopes comprising amino acids belonging to different domains of the antigen were found. The data thus obtained are compatible with those produced in previous exon-shuffling experiments, but permit a much more precise definition of recognized epitope(s).

Animals↗
PubMed1987

Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo.

We have initiated the molecular definition of the antigens recognized by Gross MuLV-specific cytolytic T lymphocytes on the surface of Gross MuLV-induced tumor cells. A panel of target cells was obtained by the double transfection and expression of a retrovirus gene and a foreign H-2 gene in recipient mouse fibroblasts. Our results show that class I H-2 transplantation antigens have a directive influence in determining the antigenicity of proteins encoded by the gag and env MuLV genes. Genes not linked to H-2 influence the intensity and the specificity of the cytolytic T lymphocyte response to Gross MuLV-induced tumors. Finally, MuLV-induced antigens expressed by transfected fibroblasts induce tumor immunity and lead to accelerated tumor rejection in vivo.

AKR murine leukemia virus↗
PubMed1985

Enhancement of tumor growth correlates with suppression of the tumor-specific cytolytic T lymphocyte response in mice chronically infected by Trypanosoma cruzi.

The immunity of BALB.B mice to syngeneic Gross murine leukemia virus (MuLV)-induced B.GV cells was studied at various times after infection by Trypanosoma cruzi. BALB.B mice chronically infected by the parasite do not develop an effective immune response against B.GV tumor cells, and B.GV tumor growth in vivo is consequently facilitated. The tumor-specific cytolytic T lymphocyte (CTL) compartment in these mice was studied in vitro because CTL are known to participate actively in syngeneic tumor rejection. These analyses showed that: a) CTL differentiation is suppressed in mice with chronic T. cruzi infections; b) suppression is at the level of CTL precursor cell activation; c) suppression is not antigen-specific; and d) suppression is mediated by macrophages and Lyt-2+ T lymphocytes.

Animals↗
PubMed1985

H-2-restricted cytolysis of L cells doubly transformed with a cloned H-2Kb gene and cloned retroviral DNA.

We report the construction of target cells by the double transformation of mouse L cells with a cloned H-2Kb gene and molecular clones of Akv or Gross murine leukemia virus (MuLV) or the cloned gag gene of Akv MuLV. Cytolytic T lymphocytes (CTL) generated in BALB.B mice specific for Gross MuLV (closely related to Akv MuLV) kill these doubly transformed cells. This is a direct indication that a CTL subpopulation recognizes H-2Kb antigen in association with a viral antigen encoded by the gag gene of Gross MuLV.

AKR murine leukemia virus↗
PubMed1984

Antigenic polymorphism of Trypanosoma cruzi: clonal analysis of trypomastigote surface antigens.

The surface membrane antigens of infectious Trypanosoma cruzi trypomastigotes were studied at the levels of the strain and of individual trypomastigote clones. Blood trypomastigotes from three T. cruzi strains, Y, CL and Tehuantepec ("Teh"), were grown in vitro by weekly infection of J774 mouse macrophage tumor cells. Each T. cruzi strain was subsequently cloned by infection of J774 cells at limited trypomastigote dilution, and antisera were produced in mice against a selection of trypomastigote clones. Criss-cross panel analyses indicated the existence of a large degree of polymorphism among trypomastigote surface antigens. Various trypomastigote surface antigens were cross-reactive, appeared to be highly conserved, and were common to the three strains considered and to all the clones derived from each strain. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that numerous trypomastigote antigenic proteins were precipitated by mouse antisera generated against cloned trypomastigotes. Some of these proteins were commonly distributed, while others were polymorphic. Finally, a state of cross-reactive immunity could be induced in C3H/He mice by infection with a cloned T. cruzi trypomastigote population. Immune mice resisted subsequent infections with lethal doses of wild-type bloodstream trypomastigotes from any one of the three T. cruzi strains.

Animals↗
PubMed1984

Synergistic protection by specific antibodies and interferon against infection by Trypanosoma cruzi in vitro.

Trypanosoma cruzi infects many mammalian cell types in vitro, including fibroblasts and macrophages. We have analyzed and compared the infection of mouse 3T3 fibroblasts and J774 macrophage-like tumor cells by cloned Y-A1.2 T. cruzi trypomastigotes. The effects of T. cruzi-specific antibodies and of interferon (IFN) on infection were considered. Specific antibodies protected 3T3 fibroblasts from infection by T. cruzi, but increased the relative infectivity for J774 cells due to binding of the opsonized parasite to J774 Fc receptors. It was also apparent that IFN-alpha, beta (produced by fibroblasts) and IFN-gamma (produced by T lymphocytes) activated trypanocidal activities in both 3T3 and J774 cells, although IFN-gamma was 100 to 2000 times more effective than IFN-alpha, beta on the basis of IFN antiviral units added per culture. When anti-T. cruzi antibodies and IFN-alpha, beta or IFN-gamma were used jointly, a synergistic protective effect was observed with both 3T3 fibroblasts and J774 cells. These results suggest that B and T lymphocytes might collaborate in vivo in the protection against T. cruzi infections by the production of anti-trypomastigote antibodies and IFN-gamma, respectively.

Animals↗
PubMed1984

Functional expression of a mouse H-2Kb gene isolated from non-expressing teratocarcinoma cells.

Embryonal carcinoma cells do not express H-2 antigens or beta 2-microglobulin. Recent studies have suggested that the expression of these antigens is likely to be controlled at the level of transcription. To study the precise organization of the corresponding genes and their possible expression in adult mouse cells, we have isolated H-2-related genes from a genomic cosmid library constructed with PCC4-aza-RI from DNA of EC cells. Clones isolated from the library after stringent hybridization with an H-2 cDNA probe were tested for their ability to direct H-2 antigen synthesis after DNA-mediated gene transfer in a fibroblastic L cell. Four clones have been found to code for the major transplantation antigen H-2Kb. Structural analysis showed that these clones contained the same entire H-2Kb gene, identical to the corresponding gene isolated from differentiated C57Bl/10 cells. Furthermore, the present studies showed that this embryonal carcinoma gene was expressed and was functional when transfected into a differentiated cell.

Animals↗
PubMed1983

Identification of a viral antigen recognized by H-2-restricted cytolytic T lymphocytes on a murine leukemia virus-induced tumor.

Monoclonal antibodies were produced against protein p30, a structural protein of murine leukemia viruses (MuLV) coded by the gag gene of MuLV. Three monoclonal antibodies of different isotypes (i.e., IgG-1, IgG-2a, and IgG-2b) were chosen for extensive analysis. These three antibodies bound to mouse tumor cells induced by Friend, Moloney, Rauscher, and Gross MuLV, but not to noninfected normal mouse spleen cells. The ability of these monoclonal antibodies to inhibit cytolytic T lymphocyte (CTL) activity by masking the antigens recognized by CTL on the target cell surface was studied in various CTL systems. It was found that the only CTL that were consistently inhibited in their lytic activity came from BALB.B (H-2b) mice immunized against syngeneic Gross MuLV-induced B.GV cells. These results thus showed that a subpopulation of BALB.B anti-Gross MuLV CTL recognized a Gross MuLV gag gene product expressed on the surface of B.GV cells.

AKR murine leukemia virus↗
PubMed1982

Specificity studies on cytolytic T lymphocytes directed against murine leukemia virus-induced tumors. Analysis of monoclonal cytolytic T lymphocytes.

The specificities of cloned cytolytic T lymphocytes (CTL) were studied for the analysis of CTL populations generated against murine leukemia viruses (MuLV) in H-2 congenic BALB/c (H-2d) and BALB.B (H-2b) mice. In particular, CTL generated in response to tumors induced by Gross MuLV and Friend MuLV were studied; these tumors expressed virus-induced antigens that do not cross-react and that can be distinguished from each other. The systematic study of 92 CTL clones clearly indicated that MuLV-immune CTL were highly heterogeneous with respect to both the intensities of target cell lysis that they mediated and to their specificity of recognition of MuLV-induced tumor target cells. Various categories of CTL clones were identified, ranging from CTL clones tht were tightly H-2 restricted and specific for the immunizing tumor to CTL clones that displayed no discernible patterns of specificity and that attacked a large number of different target cells. In addition, the surface markers of these cloned CTL were defined, and the best conditions for their prolonged maintenance in culture were determined. The present data indicate that future efforts in the definition of target antigens recognized by tumor-specific CTL should be performed with monoclonal lymphocytes.

Animals↗
PubMed1981

Quantitative variations in the expression of H-2 antigens on murine leukemia virus-induced tumor cells can affect the H-2 restriction patterns of tumor-specific cytolytic T lymphocytes.

Comparative quantitative experiments were designed to study the expression of H-2Kd and H-2Dd antigens on three different leukemia cell lines induced by Gross murine leukemia virus (MuLV)in BALB/c (H-2d) mice. The H-2 restriction patterns of syngeneic cytolytic T lymphocytes (CTL) directed against Gross MuLV-induced tumors were correlated with these quantitations of H-2Kd and H-2Dd antigens, Our results obtained by quantitative absorption of monospecific antisera indicated that the three BALB/c tumor cell lines expressed different amounts of H-2Kd and H-2Dd antigens, with H-2Dd antigen showing the greatest variability in expression because it ranged from barely detectable levels to one-eighth the amount of H-2Dd antigen expressed on normal BALB/c spleen cells. The H-2 restriction patterns of Gross MuLV-specific CTL were directly affected by these quantitative modulations in the expression of H-2Kd and H-2Dd antigens, as revealed by three independent approaches: (a) inhibition of CTL activity by monospecific anti-H-2 sera in the absence of complement; (b)competitive inhibition of CTL-mediated cytotoxicity by the addition of excess tumor cells into the reaction mixture; and (c) analysis of CTL specificities using cloned CTL populations. Our results thus indicate that H-2 restriction of tumor-specific CTL activity can be directed at the target cell level by variations in the expression of H-2 antigens.

AKR murine leukemia virus↗
PubMed1980

Studies of cloned Friend erythroleukemia tumor cells. Modulation of the tumor-specific cytologic T lymphocyte response by infectious Friend virus production in vitro.

The HFL/b tumor cell line, induced by Friend erythroleukemia virus in BALB.B mice, was used to study the relation between virus production or nonproduction and the antigens recognized by Friend virus-specific cytolytic T lymphocytes (CTL). Analysis of clones and subclones of these tumor cells revealed a high degree of heterogeneity with respect to the production and release into culture fluids of infectious Friend virus in vitro, ranging from high levels to low or undetectable levels of virus production. Although no major differences could be detected among the antibody-defined serotypes of the various clones, the susceptibility of cells of individual HFL/b clones to attack by Friend virus-specific CTL varied widely, and those clones which produced large amounts of infectious virus provided the most sensitive target cells. It was also apparent that production of infectious Friend virus was inhibitory to CTL generation in syngeneic mixed leukocyte-tumor cell cultures. Friend erythroleukemia virus-producing cells thus appeared to interact in a complex manner with the host CTL response by modulating their production of infectious Friend virus.

Animals↗
PubMed1979

Viral specificity of H-2-restricted T killer cells directed against syngeneic tumors induced by Gross, Friend, or Rauscher leukemia virus.

Cytolytic T lymphocytes (CTL) were generated against murine tumors induced by Gross, Friend, or Rauscher leukemia virus (LV) in syngeneic mixed leukocyte-tumor cell cultures. Analogous to the patterns of specificity observed with antibodies to LV-induced cell surface antigens, CTL could be classified into two major groups of specificity. Tumor cells induced by Friend, Moloney, or Rauscher virus and positive for the FMR antigen were killed by syngeneic CTL immune to any one of these three LV; the same CTL, however, were incapable of killing syngeneic tumor cells induced by Gross LV. The converse was true for Gross LV-specific CTL: these CTL were specific for syngeneic tumor cells expressing the Gross virus-associated cell-surface antigen (GCSA), and not the FMR antigen. The H-2 specificities of the two groups of LV-immune CTL were also compared, because in both cases, CTL were restricted in their killing activity to H-2-identical tumor target cells. When CTL from single strains of mice were generated against syngeneic FMR- or GCSA-positive tumor cells, differences were observed with respect both to the requirement for the expression of compatible H-2K or H-2D specificities, and to the intensity of the CTL response in congenic mice of the H-2b, H-2d, and H-2k haplotypes.

AKR murine leukemia virus↗
PubMed1979

Tumors induced by murine sarcoma virus contain precursor cells capable of generating tumor-specific cytolytic T lymphocytes.

Leukocyte fractions extracted from the tumor mass and the lymphoid organs of C57BL/6 (B6) mice carrying murine sarcoma virus-induced tumors contained primed cytolytic T-lymphocyte (CTL) precursor cells, in addition to active cytotoxic T cells. These leukocyte fractions gave a secondary response when stimulated in vitro with syngeneic tumor cells, generating large numbers of specific CTL. The activity of these CTL (H-2b) was apparently H-2-restricted, because it was ineffective on tumor targets bearing strongly cross-reacting tumor-specific antigens but with the H-2d haplotype. Furthermore, only H-2b cells bearing the Friend, Moloney, Rauscher-associated antigen, such as Rauscher leukemia virus-induced RBL-5 cells and Friend leukemia virus-induced HFL/b cells, were lysed efficiently. B male GV cells (H-2b cells induced by Gross leukemia virus) were not affected by the same CTL. We propose the existence of a dynamic state involving the migration of primed CTL precursor cells between the lymphoid organs and the tumor mass, as well as the differentiation of these precursor cells within the tumor mass into highly specific CTL.

Animals↗
PubMed1979

Cellular tumorigenicity in nude mice. Role of susceptibility to natural killer cells.

The athymic nude mouse is a useful animal model for assaying the neoplastic growth potential in vivo of animal cells transformed in vitro. Despite the demonstrated absence of thymus-dependent immunological functions, however, the nude mouse has now been shown to reject transplants of certain highly malignant heterologous tumors. In addition, a few transformed mammalian cell lines that exhibit all or most of the cellular phenotypes usually associated with malignancy fail to grow as tumors when injected into nude mice. In a continuing study to identify the in vitro phenotypes associated with tumor-forming ability in vivo, we investigated the role of cellular susceptibility to the naturally occurring, thymus-independent lymphocytes (natural killer or NK cells) in determining tumor induction by animal cells in nude mice. A representative collection of animal cells (ranging from normal human diploid cell strains to highly tumorigenic clonal cell lines, either transformed in vitro or derived from experimental tumors) was tested to see if the ability of cells to form tumors is consistently correlated with their susceptibility to NK cell-mediated lysis measured in vitro with splenic leukocytes from nude mice. If the physiological role of the NK cells in vivo were to recognize, and possibly to destroy, incipient tumor cells in situ, a direct association between cellular tumorigenicity and susceptibility to NK activity, might be expected. If, on the other hand, the formation of growing tumors by animal cells in nude mice depended on their ability to escape the cytolytic activity of NK cells, cellular tumorigenicity would be associated with cellular resistance to NK cells. Results obtained in this study failed to confirm either of these associations. Thus, cellular suscepbibility to NK cells, at least as determined by direct cytotoxicity assay in vitro, is not a useful predictive indicator of cellular tumorigenicity in nude mice.

Animals↗
PubMed1979

Suppressor T cells regulate the cytolytic T lymphocyte response to syngeneic tumors induced by murine sarcoma virus (MSV) in the mouse.

Studies were designed to analyze the immune activities of spleen cells from mice previously injected with murine sarcoma virus (MSV) and undergoing the processes of MSV tumor growth and rejection. Fractionation of MSV-primed spleen cells according to cell size by velocity sedimentation at unit gravity showed that MSV-specific cytolytic T lymphocytes (CTL) generated in vivo underwent an apparent transition in size from large to small cells as the tumor regressed. The majority of CTL precursors, however, were invariably recovered among small to medium-sized MSV-immune cells, as revealed to CTL generation in vitro in secondary mixed leukocyte-tumor cell cultures (MLTC). Evidence was obtained for the existence in MSV-immune spleens of two suppressor cell populations capable of inhibiting CTL generation in vitro: one population probably consisted of macrophages and could be removed by treatment with carbonyl iron; the second population was comprised of T cells and inhibited the differentiation of tumor-immune CTL precursors in a selective manner. These results provide a preliminary overview of the mechanisms regulating the generation, differentiation, and activity of tumor-specific CTL in a syngeneic model system.

Animals↗