The activation of IL-2 transcription in L3T4+ and Lyt-2+ lymphocytes during virus infection in vivo.

During infection of mice with lymphocytic choriomeningitis virus (LCMV), activation and proliferation of NK cells occurs early, followed by the activation and proliferation of CTL. To investigate the role of endogenously produced growth factors in mediating proliferation of these effector cell types, the transcription of IL-2 during infection was studied. We report that IL-2 is transcribed in vivo by mouse spleen cells during infection with LCMV.

Blastogenesis of large granular lymphocytes in nonlymphoid organs.

High numbers of large granular lymphocytes (LGL) accumulate in the livers and peritoneal cavities of mice during the course of viral infection. Accumulation of natural killer (NK) cells at day 3 postinfection (p.i.

Characterization of green hams from Iberian pigs by fast analysis of subcutaneous fat.

Melting point, slip point, iodine value (fast analyses) and percentage contents of fatty acids were determined in subcutaneous fat of hams from Iberian pigs in order to study the possibilities of characterizing the type of pig feeding and the relationships between the results of fast analysis and fatty acid contents. Both types of analyses showed important differences between samples from pigs fed on acorn and samples from pigs fed on mixed feeds. When a combination of feeding materials (acorn and mixed feeds) was used, the analyses gave intermediate results, closer to those obtained with mixed feeds only.

Murine natural killer cells stimulated in vivo do not express the T cell receptor alpha, beta, gamma, T3 delta, or T3 epsilon genes.

Murine blast natural killer (NK) cells responding to in vivo stimulation were isolated and characterized as to their expression of the T cell receptor (TCR) variable genes alpha, beta, and gamma and the TCR constant genes T3 delta and T3 epsilon. In vivo stimulated blast T cells were isolated for comparison. RNA extracted from highly purified blast cell populations elicited in vivo was probed for TCR transcripts by Northern blot analysis.

Aberrant T cells in beige mutant mice.

Cytotoxic T lymphocyte (CTL) morphology and function was examined in beige (bg/bg) mutant mice during infection with lymphocytic choriomeningitis virus (LCMV). Virus-specific, class I-restricted CTL activity mediated by total spleen leukocytes isolated from bg/+ or +/+ mice on days 7 or 9 postinfection with LCMV was moderately higher than that mediated by spleen cells isolated from bg/bg mice. The CTL generated in bg/bg mice had aberrant morphology.

Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells.

Diabetes-prone BioBreeding/Worcester (BB/Wor) rats received thrice weekly injections of mAb against antigens expressed on the surface of all T cells (OX19), cytotoxic/suppressor, and NK cells (OX8), helper/inducer cells (W3/25, OX35, OX38), and Ia+ cells (OX6, 3JP, OX17). Treatment with OX8 or OX19 achieved stable reductions of splenic and peripheral blood NK cells and helper/inducer T lymphocytes, respectively, and protected against diabetes. OX19 injections also prevented lymphocytic insulitis, thyroiditis, and the synthesis of autoantibodies to thyroid colloid and smooth muscle antigens.

Natural killer cell number and function in the spontaneously diabetic BB/W rat.

The BB/W rat provides a good model of spontaneous autoimmune diabetes. Diabetes-prone (DP) rats have a virtual lack of OX 8+ OX 19+ T cytotoxic/suppressor cells in peripheral blood lymphocytes (PBL) and spleen, suggesting that the OX 8+ OX 9- natural killer (NK) cells are the predominant cytotoxic cell in this animal. In this study, we have shown that rat NK cells belong to the OX 8+ OX 19- asialo GM1 bright population, and that rat NK cell function may be depleted in vivo by administration of OX 8 antibody.

Purification and target cell range of in vivo elicited blast natural killer cells.

Blast natural killer (NK) cells were elicited in the spleens of mice by treatments with the interferon inducers lymphocytic choriomeningitis virus (LCMV) or polyinosinic-polycytidylic acid (poly I:C). The blast-NK cells, separated on the basis of size by centrifugal elutriation, were compared with blast cytotoxic T lymphocytes (CTL) generated during infection with LCMV. In vivo treatments with antibody to asialo GM1 (AGM1) blocked the appearance of blast-NK cells but not blast-CTL.

Generation of large granular T lymphocytes in vivo during viral infection.

Cytolytic lymphocytes were isolated from the spleens of lymphocytic choriomeningitis virus (LCMV)-infected mice and were characterized in regards to function, cell size, antigen phenotype, and cell morphology. Only 2% of the Lyt-2+ cells from uninfected mice were large granular lymphocytes (LGL), whereas 21% of the Lyt-2+ cells isolated 7 days postinfection were LGL. The day 7 Lyt-2+ populations contained all of the LCMV-specific, class I histocompatibility antigen-restricted cytotoxic T lymphocyte (CTL) activity, but no natural killer (NK) cell activity.

Lysis of uninfected and virus-infected cells in vivo: a rejection mechanism in addition to that mediated by natural killer cells.

To examine the lysis of virus-infected cells in vivo, uninfected and lymphocytic choriomeningitis virus (LCMV)-infected L-929 cells were labeled in vitro with [125I]-iododeoxyuridine and implanted intravenously into mice. Natural cytotoxicity against both uninfected and virus-infected cells was demonstrated in normal uninfected mice, but LCMV-infected cells were cleared from the lungs and whole bodies more rapidly than uninfected cells. Treatment of L-929 cells with defective interfering LCMV inhibited standard virus synthesis and protected the target cells from enhanced in vivo rejection.

Mononuclear phagocyte maturation: a cytotoxic monoclonal antibody reactive with postmonoblast stages.

The rat IgM monoclonal antibody B23.1 was found to bind to mononuclear phagocytes that had matured beyond the monoblast stage. Macrophages from several anatomical sites, elicited by different means, as well as those cultured from bone marrow precursors, bound B23.

Interferon induces natural killer cell blastogenesis in vivo.

Interferon (IFN), types beta and gamma, and IFN inducers polyinosinic-polycytidylic acid and lymphocytic choriomeningitis virus all stimulated the generation of blast-NK cells in mouse spleens. Blast-NK cells were characterized on the basis of size, 3H-thymidine uptake, and NK cell markers. These data indicate that in addition to augmenting NK cell-mediated lysis, IFN may regulate NK cell proliferation in vivo.

Increase in NK cell number and turnover rate during acute viral infection.

NK cell turnover and division during infection of mice with lymphocytic choriomeningitis virus (LCMV) was examined. Treatments with hydroxyurea (HU), a drug specific for cells synthesizing DNA, had no effect on control spleen NK cells, but significantly reduced NK cell-mediated lysis in LCMV-infected mice. When HU was administered at 9 and 2 hr before spleen cell harvest, the augmented lysis mediated by NK cells isolated from LCMV-infected mice was only 40% of that mediated by NK cells isolated from LCMV-infected untreated mice.

Elevated natural killer cell-mediated cytotoxicity, plasma interferon, and tumor cell rejection in mice persistently infected with lymphocytic choriomeningitis virus.

To assess the effects of chronic virus infection on NK cells, the related phenomena of interferon (IFN) production, NK cell activation, and resistance to tumor implants were studied in mice persistently infected with lymphocytic choriomeningitis virus (LCMV). NK cells from these LCMV-carrier mice displayed augmented killing of the NK-sensitive YAC-1 target cell. They did not lyse the more resistant targets L-929 and P815, whereas NK cells from acutely infected mice efficiently lysed all three cell types.

Activation and role of natural killer cells in virus infections.

Natural killer cells may play a significant role in virus infections. Virus-induced interferon activates these cells to become highly cytotoxic, and viral infections may also affect the proliferation of such cells. Non-immune mice have an apparently cellular defense mechanism which rapidly lyses implanted virus-infected cells.

Interferon production and activation of non-specific effector cells by stimulation with lymphoblastoid cell lines in vitro.

A population of non-specific effector lymphocytes is generated in response to stimulation with lymphoblastoid cell lines (LCL). These cytotoxic cells have an activity analogous to that exhibited by natural killer (NK) cells. When lymphoid cells lines established by transformation with Epstein-Barr virus (EBV) are used to stimulate autochthonous T-cell-enriched lymphocytes, the activity against the NK-sensitive target, K562, is increased up to 14-fold.