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J A Frelinger

Publications and source records attributed to J A Frelinger.

At least 127 records · Page 7Linked to original sources
PubMed1982

Macrophage antiviral activity: extrinsic versus intrinsic activity.

Peritoneal exudate cells from strains of mice both resistant and susceptible to challenge with mouse hepatitis virus strain JHM were examined for extrinsic and intrinsic antiviral activity. Thioglycolate-elicited and resident peritoneal cells from uninfected mice were able to suppress viral growth in a permissive cell. The active cell in both populations is an adherent, radiation-resistant, Thy-1.2 antigen- and Ia antigen-negative cell. The suppression of virus replication was not related to nonspecific cellular cytotoxicity directed against the permissive host cell, and no interferon was detected. The expression of extrinsic antiviral activity was not related to the ability of the host to resist mouse hepatitis virus infection by virtue of either age or genetic background. The expression of intrinsic antiviral activity, on the other hand, correlated with the ability of the host to resist virus challenge, indicating a characteristic distinction between these two in vitro mechanisms of macrophage-mediated antiviral activity with regard to host resistance to viral infection. Further, the ability of a macrophage to support viral replication itself was independent of the ability of the macrophage to suppress virus growth in another cell.

Aging↗
PubMed1982

Construction of microcell hybrid clones containing specific mouse chromosomes: application to autosomes 8 and 17.

Fibroblast cultures prepared from mice homozygous for a Robertsonian translocation (centric fusion) between autosomes 8 and 17 [Rb(8.17)] were used as donors in microcell-mediated chromosome transfer experiments. By using hamster recipient cells deficient in adenine phosphoribosyltransferase (APRT-) and selecting for expression of murine APRT (a chromosome 8 marker), microcell hybrids were isolated which retained only the mouse Rb(8.17) translocation in addition to the hamster chromosome complement. The translocation was stable in cells maintained under APRT+ selective pressure, and mouse marker traits encoded by genes on both chromosomes 8 and 17 segregated concordantly. A second family of hybrid clones was constructed by fusing microcells derived from wild-type mouse fibroblasts with APRT- hamster cells. Four of six clones analyzed retained only mouse chromosome 8. These studies demonstrated that microcell hybrids containing specific Robertsonian translocations as the only donor-derived genetic material can be obtained. Furthermore, a number of Robertsonian translocations between chromosomes which carry selectable markers (chromosomes 3, 8, and 11) and other autosomes have been described. By using fibroblast cultures prepared from mice containing these translocations as donors in microcell fusions, 18 of the 20 mouse chromosomes could be selectively fixed in different hybrid clones. Thus, a collection of 20 hybrid clones, each containing a single, specific mouse chromosome, can be constructed by using the strategy described in this report. The potential utility of such a monochromosomal hybrid panel is discussed.

Adenine Phosphoribosyltransferase↗
PubMed1981

Structure of murine Ia antigens. Two dimensional electrophoretic analyses and high pressure liquid chromatography tryptic peptide maps of products of the I-A and I-E subregions and of an associated invariant polypeptide.

We demonstrate that an invariant polypeptide, first described by Jones et al. (21), co-immunoprecipitates with our Ia molecules, that its interaction with Ia polypeptides varies with haplotype, and that it is not a precursor of the Aalpha, Abeta, Ealpha, or Ebeta. polypeptides. We also show that the polypeptides that we have previously characterized are contaminated with very little, if any, invariant protein. Further, we have used our high-pressure liquid chromatography tryptic peptide map technique to formally map the genes encoding Aalpha, Abeta, and Ebeta to the I-A subregion using recombinant and F1 hybrid mice.

Animals↗
PubMed1981

Peptide map comparisons of epidermal and spleen H-2 molecules.

Peptide map comparisons of molecules encoded in the mouse H-2 complex isolated from epidermal cell preparations have been carried out. We previously showed that the Ia molecules from both the I-A and I-E subregions are synthesized by nonlymphoid bone-marrow-derived cells, probably Langerhans cells. The K and D or transplantation molecules are synthesized by both "true" epidermal cells and nonlymphoid bone-marrow-derived cells. The tryptic maps generated by separating tryptic peptides by high pressure liquid chromatography (HPLC) of epidermal H-2 molecules are identical to their spleen-cell counterparts. The biological significance of this finding is discussed.

Animals↗
PubMed1981

Macrophages and resistance to JHM virus CNS infection.

Thioglycollate elicited peritoneal exudate cells from resistant SJL mice, younger susceptible SJL mice, and susceptible ASW, BALB/c, and C57/BL6 mice all exhibit extrinsic antiviral activity. The active cell was characterized as a Thy 1.2 negative, Ia negative, radiation resistant adherent cell. The antiviral activity was not due to nonspecific cellular cytotoxicity directed against the susceptible cell nor interferon. Adherent PE cells from resistant and susceptible SJL mice were similar with respect to the number of phagocytes, nonspecific esterase containing, Fc, and C3b receptor bearing cells. Finally, extrinsic antiviral activity was not dependent upon intrinsic antiviral activity.

Age Factors↗
PubMed1981

Tryptic peptide map analyses of mouse transplantation antigens.

Tryptic peptide map analyses of five K- and three D-gene products of various H-2 haplotypes are presented. These data support earlier sequence studies and demonstrate that the variations in allelic gene products of the K or D loci are scattered throughout much of the polypeptide chains. Furthermore, the K allelic gene products are no more closely related to one another than they are to the D allelic gene products. This apparent lack of K-ness and D-ness places interesting constraints on the genetic organization and evolutionary history of the genes encoding the transplantation antigens.

Amino Acids↗
PubMed1981

Expression and synthesis of murine immune response-associated (Ia) antigens by brain cells.

This paper provides biochemical and histochemical evidence that a fraction of murine brain cells express and synthesize Ia (Immune response-associated) antigens. Both I-A and I-E subregion products are detected on frozen sections of mouse brains by immunoperoxidase staining. Most of these Ia-bearing cells are located in white matter tracts and appear to be intrafascicular oligodendrocytes. In contrast, cells in the gray matter rarely display detectable Ia antigens on their cell surfaces. Specificity of the staining was confirmed by absorption studies. Biochemical evidence for the active synthesis of Ia antigens by brain cells was obtained by immunoprecipitation of [3H]leucine/tyrosine-labeled, NP-40-extracted cell lysates with monoclonal anti-Ia reagent. Both the alpha and beta subunits of Ia antigens were identified by NaDodSO4 electrophoresis. By contrast, anti-mu serum failed to precipitate any product, thus eliminating contaminant B lymphocytes as a source of Ia antigens.

Animals↗
PubMed1981

T lymphocyte responses to non-H-2 histocompatibility antigens. I. Role of Ly-1+2+ T cells as cytotoxic effectors and requirement for Ly-1+2+ T cells for optimal generation of cytotoxic effectors.

Cytotoxic effector T cells specific for non-H-2 histocompatibility (H) antigens were examined for phenotypic expression of lymphocyte differentiation (Ly) antigens. Virtually all H-Y-specific cytotoxic effectors generated in mixed lymphocyte culture were Ly-1+2+ T cells. H-3-specific effectors comprised both Ly-1+2+ and Ly-1-2+ T cells. However, cytotoxic effectors specific for multiple non-H-2 H antigens were predominantly Ly-1-2+ T cells. The optimal generation of H-Y- and H-3-specific effectors required Ly-1+2+ T cells; optimal generation of multiple non-H-2 H antigen-specific effectors required an interaction between Ly-1+2- and Ly-1-2+ T cells. These observations suggest that the identity of the target H antigen in part determines the Ly type of responsive T cells. Our observations suggest that 2 alternative pathways of T cell response exist for non-H-2 H antigens. The first pathway involves an interaction between Ly-1+2- helper T cells and Ly-1-2+ cytotoxic effector precursors. The 2nd pathway simply involves the response of Ly-1+2+ T cells proliferating and generating H antigen-specific cytotoxic effectors.

Animals↗
PubMed1980

Role of self carriers in the immune response and tolerance. V. Reversal of trinitrophenyl-modified self suppression of the B-cell response by blocking of H-2 antigens.

Trinitrophenylated syngeneic spleen cells (TNP-SC) are potent tolerogens of the anti-TNP plaque-forming cell (PFC) response in vivo and in vitro. This unresponsive state requires T cells for both its induction and maintenance. Because H-2K/D-restricted cytotoxic T cells are also induced by exposure to TNP-SC, we determined the role(s) of histocompatibility antigens (K, I, and D) in the suppression of the PFC response by TNP-SC. We treated syngeneic TNP-modified stimulator cells with antiserum directed at K-, I-, or D-region determinants and found that blocking of H-2K or D antigens on TNP-SC transformed these tolerogens into immunogens capable of eliciting an anti-TNP PFC response in the absence of extrinsic immunogens like TNP-polymerized flagellin. In H-2k or H-2a(k/d) mice, only H-2Kk needs to be blocked on the stimulator cells, whereas H-2K or D recognition was apparent in B10.A(4R) mice. These observations indicate that suppression of the PFC response by TNP-SC shows the same restriction in recognition as does the cytotoxic T-cell response. Furthermore, our results suggest that TNP-I-A is recognized by the helper cells in this system as the intrinsic antigen. When both TNP-K and TNP-I-A are present and available on the same stimulator cell, suppression (via modified K recognition) is dominant over help.

Animals↗
PubMed1980

Multiple H-2 and non-H-2 genes controlling the antilysozyme response: alternative gene constellations can lead to responsiveness.

Mice carrying the H-2b and H-2s haplotypes are genetically nonresponsive to hen egg-white lysozyme (HEL). Analysis of the anti-HEL response patterns of F1, F2 and backcross progeny showed that responsiveness was dominant and H-2 linked. From plaque-forming cell and serum assays in intra-H-2 recombinant mice, it was established that two I loci were implicated, the possession of either leading to responsiveness to HEL. One of the I genes maps in I-A, and the second in I-C, S or G. While the nonresponse phenotype was determined by the H-2 haplotype, there were codominant non-H-2 genes which contributed to a severe reduction in the level of antibody produced in responder strains. A model is presented attributing the outcome of an encounter with HEL to the regulatory balance of helper and suppressor T cells, which have been activated by different subregions of the major histocompatibility complex.

Animals↗
PubMed1980

Characterization of responding cells in oxidative mitogen stimulation. III. Presence of I-A- and I-J, E, C-subregion gene products on the surface of required cells.

Ia antigens coded by genes of the murine major histocompatibility complex are expressed on the surface of a population of cells critical to the proliferative response of murine spleen cells to the oxidative mitogen neuraminidase/galactose oxidase. By selective depletion with antiserum and complement, Ia antigens coded (or determined) by the I-A and I-J, E, C subregions of the Ir region can be detected on the surface of cells required for the response. In addition, I-A-subregion products have a functional significance in cellular activation which can be demonstrated by blocking experiments with anti-Ia serum in the absence of complement.

Animals↗
PubMed1980

Bone marrow origin of Ia molecules purified from epidermal cells.

Using radiation bone marrow chimeras, we have shown that Ia molecules purified from epidermal cell preparations of the mouse reflect the Ia phenotype of the bone marrow donor. This result strongly suggests that Ia molecules are synthesized by a bone-marrow-derived cell in the epidermis. Furthermore, results of peptide map analysis of immunoprecipitated biosynthetically labeled Ia suggest that the Ia molecules found in skin are identical to those found on B lymphocytes. These results support biochemical as well as serologic identity.

Animals↗
PubMed1980

Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM. II. Adherent cell-mediated protection.

Resistance of SJL/J mice to intracranial inoculation with the JHM strain of mouse hepatitis, a coronavirus, is dependent upon the age of the animals at inoculation. Animals 12 weeks of age or older are resistant, whereas those 6 weeks or younger are uniformly susceptible to viral infection. Spleen cells or thioglycolate elicited peritoneal exudate cells can transfer resistance from 12-week-old to 6-week-old recipients. Removal of the adherent cells from either spleen or peritoneal cells ablated protection. Adherent cells from 12-week-old mice were protective even after depletion of Ia- and Thy-1-bearing cells. Antiviral antibody, thioglycolate injection into 6-week-old animals, and nylon wool-purified T cells were ineffective in mediating resistance. Adherent cells transferred 4 days before virus challenge, but not after challenge, were protective. Thus, there is an age-related change in SJL mice that protects from acute central nervous system disease, which may be due to maturation of a specialized adherent cell population.

Aging↗
PubMed1980

Characterization of responding cells in oxidative mitogen stimulation. I. Ia+ cells and Ly-1+2+ cells are required for the proliferative response.

Addition of anti-Ia sera to cultures of mouse spleen cells stimulated with oxidative mitogens, neuraminidase/galactose oxidase (NaGO) or sodium periodate (NaIO4), inhibits the subsequent proliferative response 30 to 70%. Anti-H-2K or D sera were not specifically inhibitory. Similar inhibition was seen when cells were pretreated with anti-Ia sera and washed before exposure to the mitogenic enzymes. Treatment with anti-Ia serum and complement depletes greater than 89% of the NaGO and the NaIO4 responses but 2% or less of the phytohemagglutinin (PHA) response. The response to NaGO was sensitive to depletion with anti-Thy-1 serum, rabbit anti-mouse brain serum, anti-Ly-1, or anti-Ly-2 serum. Mixtures of Ly-1 and Ly-2-depleted populations did not restore responsiveness. Thus both an Ia+ cell and an Ly-1+2+ T cell are required for [3H]TdR incorporation in response to NaGO treatment.

Animals↗
PubMed1980

Characterization of responding cells in oxidative mitogen stimulation. II. Identification of an Ia-bearing adherent accessory cell.

Treatment of murine lymph node or spleen cells with anti-Ia serum and complement (C), depletes the subsequent proliferative response of the residual cells to the oxidative mitogen galactose oxidase (NaGO). Restoration of the mitogenic response could be achieved by the addition of adherent accessory cells prepared by a variety of techniques. Loosely adherent dendritic cells were the most efficient population of restoring cells. Treatment of adherent cells with anti-Ia serum and C removed their capacity for restoration. Restoration of the oxidative mitogen response to lymph node cells depeleted of adherent cells by passage over nylon wool and Sephadex columns was similar to restoration of Ia- depleted lymphocyte populations. Further NaGO-induced lymphocyte transformation requires an Ly-1+2+ T lymphocyte and an Ia-positive adherent accessory cell.

Animals↗
PubMed1979

T lymphocyte response to H-2 mutants: cytotoxic effectors are Ly-1+2+.

The lymphocyte differentiation (Ly) antigen phenotype of cytotoxic effector T cells specific for H-2 mutant alloantigens was determined. Cytotoxic effectors generated in primary mixed lymphocyte culture and specific for H-2Kba and H-2Dda alloantigens are sensitive to both anti-Ly-1 and anti-Ly-2 serum plus complement. Reconstitution analysis demonstrated that the mutant-specific T cells were Ly-1+2+. These observations and those previously reported, which indicated that H-2K/D mutant-specific T cells proliferating in mixed lymphocyte culture were Ly-1+2+, demonstrated that Ly-1+2+ T cells are immunocompetent. Furthermore, the nature of the stimulating H-2 complex alloantigen determines the Ly phenotype of responsive T cells.

Animals↗