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R B Levy

Publications and source records attributed to R B Levy.

83 records · Page 5Linked to original sources
PubMed1979

Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. I. Preferential in vitro responses to trinitrophenyl-modified self K- and D-coded gene products in parental and F1 hybrid mouse strains.

Spleen cells from H-2b,k,d C57Bl/10 congenic mice were sensitized in vitro to trinitrobenzenesulfonate (TNBS)-modified autologous spleen cells. Cold target competition studies at the lytic phase demonstrated three distinct patterns of cytotoxic responsiveness: (a) H-2b spleen cells generated approximately equivalent CTL responses against Kb and Db modified self products, (b) H-2d spleen cells generated preferential responses against Dd modified self products, and (c) H-2k spleen cells generated cytotoxic responses which could only be detected against Kk self products in association with TNP. F1 spleen cells were sensitized against autologous TNBS-treated cells. The results showed that, although H-2b parental cells generated approximately equivalent Kb-TNP- and Db-TNP-specific CTL, the presence of the H-2b haplotype did not result in the generation of (a) Dk-TNP CTL response by (H-2b x H-2k) spleen cells, nor (b) a Db CTL response by (H-2b x H-2a) F1 spleen cells. Additionally, (H-2d x H-2k) F1 cells failed to generate detectable Dd-TNP-specific CTL, although H-2d parental cells generated D-regional-specific CTL. The findings demonstrated that these F1 response patterns paralleled those of the H-2k and H-2a parents, i.e. weak or no D-region TNP-specific CTL were induced. Because (H-2d x H-2a) F1 responders stimulated with H-2d TNBS-treated cells did generate good Dd TNP responses, the results illustrated that the presence of responder genes was not sufficient to result in a D-region TNP CML. It is suggested that the absence of Kk alleles on the stimulating population is necessary for the generation of D-region TNP CTL in these F1's. Mechanisms which could account for these response patterns in parental F1 mice are discussed including immunodominance, suppression, T-cell response , and Ir-gene defects.

Animals↗
PubMed1979

Cross-reactivity among the products of three nonallelic H-2 loci, H-2Ld, H-2Dq, and H-2Kk.

Cross-reactions of the products of three nonallelic H-2 loci, H-2K, H-2D, and H-2L, have been studied by serological, immunochemical, and cellular immune techniques. Immunoprecipitation experiments revealed a determinant shared between Ld and Dq molecules but absent on Dd molecules, By cytotoxic screening of sera from individual mice an exceptional anti-Ld serum was found which cross-reacted with an H-2k antigen. Genetic mapping studies suggested that the basis of this activity was an Ld-Kk serological cross-reaction. Cytotoxic T cells generated to Ld alloantigens were also found to recognize a cross-reacting Kk determinant. These studies therefore suggest that L, D, and K are three structurally homologous cell surface glycoproteins that have evolved from a common primordial gene.

Animals↗
PubMed1979

Studies on in vivo priming of the TNP-reactive cytotoxic effector cell system. I. Comparison of the effects of intravenous inoculation with TNP-conjugated cells on the development of contact sensitivity and cell-mediated lympholysis.

A comparison was made of the effects of i.v. inoculation of trinitrophenyl-(TNP) conjugated syngeneic cells on the subsequent in vitro generation of TNP-reactive effector cell activity and on the in vivo development of TNP-contact sensitivity. The administration of syngeneic TNP-conjugated spleen cells before 2,4,6-trinitro-1-chlorobenzene (TNCB) painting abolished the capability of animals to develop TNP-contact sensitivity. In contrast, the same treatment resulted in an appreciable augmentation in the generation of TNP-reactive cytotoxic effector cell activity as measured by subsequent in vitro sensitization with TNP-conjugated cells. The possible mechanisms by which enhanced TNP-reactive cytotoxic effector cell activity was elicited under conditions identical to those that induced unresponsiveness for TNP-contact sensitivity are discussed.

Animals↗
PubMed1978

Involvement of H-2L gene products in virus-immune T-cell recognition. Evidence for an H-2L-restricted T-cell response.

The H-2L locus is closely linked to H-2D and codes for antigenic specificities present on a 45,000 mol wt glycoprotein that is distinct from the molecule which bears the D region private specificity. It was found that BALB/c-H-2db mice, which lack detectable cell-surface H-2L gene products, were able to generate influenza- and vaccinia-immune cytotoxic T cells which lyse D region-compatible target cells, although they have been reported to be incapable of making a similar response to ectromelia virus (7). Thus, the lack of H-2L antigenic specificities does not produce a general loss of responsiveness for other viruses even when a highly cross-reactive pox virus (vaccinia) was studied. Antisera-blocking experiments utilizing sera specific for either L or D molecules indicated that BALB/c mice generate influenza virus-immune cytotoxic T-cell subsets which independently recognize H-2L and H-2D gene products in association with viral antigens. These results are the first indication that products of the H-2L locus can operate analogously to H-2K/D gene products in virus-immune T-cell recognition.

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PubMed1978

Alloantigens determined by a second D region locus elicit a strong in vitro cytotoxic response.

The newly defined L antigen (previously designated D') has been studied with the CML assay. Balb/c-H-2db mice, which carry a loss mutation in the D region, were found to generate anti-L cytotoxic effector cells when stimulated with wild-type (BALB/c) cells. When the target cells were treated with an antiserum against L, cytolysis by BALB/c-H-2db anti-BALB/c effectors was completely blocked. However, an antiserum against D, the antigen that bears the D region private specificity, had no effect on the anti-L cytotoxic response. In a control CML experiment that was specific for the D antigen, the antiserum to L had no effect, whereas the antiserum to D blocked completely. These results indicate that the L and D antigens are recognized in a CML response as separate entities on the cell surface. In an allogeneic response to the products of the D region, cytotoxic effectors were generated that were specific for L in addition to those specific for D. This conclusion was supported by blocking experiments with either antisera or unlabeled targets. These functional studies thus extend previous co-capping and immunochemical studies, and further support the hypothesis that L is a third transplantation antigen similar to the K and D antigens.

Animals↗
PubMed1978

Properties of H-2L locus products in allogeneic and H-2 restricted, trinitrophenyl-specific cytotoxic responses.

The role of the recently defined L antigen (a second D region product) in allogeneic and TNP-specific syngeneic primary CML responses has been investigated. The lysis by anti-L specific cytotoxic effector cells was not inhibited when the target cells were pretreated with an antiserum directed against K and D, whereas an antiserum against L completely abrogated this response. Therefore, H-2L products are recognized on the target cell independently of H-2K and H-2D locus products. Both A.SW cells as well as B10 cells were found to respond to Ld alloantigens, in addition to Dd alloantigens when stimulated by cells differing only in the D region. The results of cold target blocking and antiserum inhibition experiments failed to detect cytotoxic cells with specificity of L antigens in association with TNP, under conditions in which TNP-specific effectors to K and D antigens were demonstrable. These findings suggest that there is a more limited involvement of H-2L locus products than the H-2K or H-2D locus products in the induction and specificity of these responses.

Animals↗
PubMed1977

Control of immunity in parental and F1 hybrid mouse strains to a spontaneously arising parental tumor. I. Correlation between in vitro and in vivo anti-tumor reactivity in responsive and unresponsive animals.

This study has investigated the in vivo and in vitro cellular immunity of the AKR/J, (AKR/J x C57BL/6)F1 and (AKR/J x DBA/2)F1 mouse strains to a spontaneously arising AKR/J tumor. The study concludes that: 1) there is an excellent correlation between the growth of the tumor in vivo, and the ability of spleen cells from the respective strains to generate both primary and secondary cell-mediated cytotoxic responses in vitro; and 2) one F1 host can be considered a responder against this tumor, whereas the other F1 strains studied appears to be genetically nonresponsive. Possible mechanisms relating to the observed patterns of response are discussed.

Animals↗
PubMed1976

Correlation of suppressor cell development in parental and F1 hybrid mouse strains with the growth of a parental tumor in vivo.

Parental AKR/J, and AKB6F1 and AKD2F1 hybrid mice were injected subcutaneously with a spontaneously arising AKR/J tumor. The highly responsive AKB6F1 strain never exhibited any depression of immune functioning during the course of tumor growth and regression. The (AKR/J) intermediately responsive strain, while able to generate a successful anti-tumor response, did display a transient reduction of immunological capability, but only during the period tumor growth and not during tumor regression. Cells able to suppress antibody, but not cell-mediated responses, were found. The unresponsive AKD2F1 strain was characterized by both a marked depression of immune responsiveness, as well as the generation of suppressor cells to both antibody, and later, cell-mediated responses. Depression of immune responsiveness, and the generation of suppressor cells, appeared to correlate with the strength or weakness of the anti-tumor response in these strains of mice.

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PubMedDate not supplied

Rat thyroid epithelial cells provide limited accessory function but fail to present allo antigens in vitro.

Human and mouse thyroid epithelial cells (TEC) have been reported to exhibit a number of immunological activities including partial, but not total, antigen presenting capability. In the studies described here, the thyroid stimulating hormone-dependent rat thyroid epithelial cell line FRTL-5 was tested for its abilities to provide accessory and antigen presenting cell (APC) activity. FRTL-5 cells alone were not able to function as accessory cells for ConA induced polyclonal proliferation of purified T-cells and were not capable of inducing alloreactive T-cell proliferation in mixed lymphocyte reaction (MLR) cultures. Furthermore, even following the induction and enhanced expression of MHC class II and class I MHC products, respectively by IFN-gamma, FRTL-5, cells could not function as accessory cells or induce alloreactive T-cell proliferation as the singular stimulatory population in MLR cultures. However, these epithelial cells could effectively synergize with either low numbers of spleen cells, or with supernatants from activated T-cells, to provide accessory function in ConA stimulated cultures. These findings suggest that hormone-dependent and functional rat TEC cannot directly activate resting syngeneic or unprimed allogeneic T-cells, although they can provide at least one accessory cell signal involved in T-cell activation by mitogen. Thus, the results presented here do not support contentions that such a nonhemopoietic resident cell population is capable of directly triggering the initial activation of anti-thyroid specific T-cells.

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