Natural immunity and cell growth regulation 

About: Natural immunity and cell growth regulation is an academic journal. The journal publishes majorly in the area(s): Natural killer cell & Cytotoxic T cell. It has an ISSN identifier of 0254-7600. Over the lifetime, 205 publications have been published receiving 2573 citations.

Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines.

Abstract: In this report, we show that in vitro stimulation of human peripheral blood mononuclear cells (PBMC) with B lymphoblastoid cell lines results in preferential proliferation of cells with the phenotypic, genotypic and functional characteristics of natural killer (NK) cells. This culture system offers a useful method for obtaining large numbers of pure NK cells on which biochemical, molecular and functional studies can be performed. Using this culture system, and average 25-fold increase in NK cell number is obtained, whereas the number of T cells is increased only 3-fold. At early times, activation of both T and NK cells occurs, as detected by the presence of activation antigens on both cell types, but actual proliferation of NK cells starts on day 6 of culture. Elimination of CD3(+)/CD5(+) T cells from the cultured cells gives homogeneous preparations of large numbers of CD16(+)/NKH-1(+) cells that have the morphology of large granular lymphocytes, are powerful effectors of both spontaneous and antibody-dependent cell-mediated cytotoxicity, and rapidly proliferate in the presence of recombinant interleukin 2 (rIL-2). As fresh NK cells, NK cell-enriched preparations from 10-day cultures of Daudi-stimulated PBMC do not show rearrangement of the gene for the beta-chain of the T cell antigen receptor; the 1.3-kb functional transcript of the beta-chain gene was not expressed in NK cells, but the 1.0-kb truncated transcript was present in all preparations. Our data indicate that proliferation of both T and NK cells is dependent upon IL-2 production in the culture, because an anti-IL-2 antiserum completely suppresses proliferation. Because T cells, and in particular CD4(+) T cells, are required for preferential proliferation of NK cells, the NK cell stimulation induced by the B cell line is probably in part indirect, and due to induction of IL-2 production by allogeneic stimulation of CD4(+) cells. However, the B cell lines also need to interact directly with NK cells because neither allogeneic PBMC nor high doses of rIL-2 are sufficient to induce preferential proliferation of NK cells.

A leukocyte subset bearing HLA-DR antigens is responsible for in vitro alpha interferon production in response to viruses.

Abstract: In this report, we characterize the major human peripheral blood nonadherent mononuclear cell subset that is responsible for the production in vitro of alpha-interferon (alpha IFN) in response to influenza, Sendai, and Newcastle disease viruses. Using a panel of anti-monocyte, anti-B, anti-T and anti-natural killer cell monoclonal antibodies to purify and recover both positive and negative cell populations, we show that the major alpha IFN-producing cells are HLA-DR(+) cells with no other surface markers characteristic of either lymphocytes or myelomonocytic cells. These cells copurify, on Percoll density gradients, with cells mediating NK activity, but the cell population responsible for alpha IFN production can be distinguished unambiguously from NK cells based on the former's reactivity with an anti-HLA-DR monoclonal antibody, the lack of reactivity with antibodies that detect the low-affinity receptor for IgG on human natural killer cells and granulocytes, and the inability to mediate spontaneous cytotoxicity. Double immunofluorescence assays indicate that cells of this subset, the lineage of which is as yet undetermined but which might be related to dendritic cells, constitute a minor proportion (approximately 1-1.5%) of the nonadherent mononuclear cells from healthy donors.

Stress and morphine affect survival of rats challenged with a mammary ascites tumor (MAT 13762B).

Abstract: We have previously shown that exposure to inescapable footshock stress decreases survival of rats injected with a mammary ascites tumor (MAT 13762B). This increased vulnerability to the tumor challenge was prevented by an opiate antagonist, naltrexone, suggesting mediation by opioid peptides. Supporting this hypothesis, we now report that a high dose of an opiate agonist, morphine, also reduces survival of rats given the same tumor. This effect shows tolerance after 14 daily injections. The adverse effect of stress, however, did not show other signs of opioid involvement: it manifested neither tolerance with repeated stress exposures nor cross-tolerance in morphine-tolerant rats. Our recent findings that stress and morphine reduce natural killer cell cytotoxicity in a similar fashion suggest an immune mechanism that may explain the present results.

Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity.

Abstract: In recent studies of 'low natural killer (NK) cell syndrome', low NK activity was measured in individuals who were symptomatic, and therefore a causal relationship between low NK activity and infectious or other disease manifestations could not be concluded. However, preliminary work by members of our collaborative team (S.L. and R.H.) provided some indications for chronic low NK activity preceding and predicting subsequent infectious morbidity. This present study was designed to address this causal question in a larger sample, using a longitudinal design. Subjects were 106 healthy normal volunteers from the community. They were examined medically and psychosocially at baseline, and were then followed over a 6-month interval, with serial monthly assessments over the study period. The results supported our hypothesis that individuals who were currently healthy, but who exhibited a pattern of natural immunity characterized by persistently low NK cytotoxicity would be at risk for development of infectious sequelae over a 6-month follow-up period. The results also showed that younger age and the perception of more severe 'hassles' or stressors also predicted more infectious morbidity during the 6-month study period. Chronological age appeared to have both a direct, as well as indirect (via NK activity) association with illness outcome. Contrary to our expectation, the report of environmental stressors was directly associated with illness outcome, but not indirectly associated with outcome via natural immunity.