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Biomedical subjects

T Folks

Publications and source records attributed to T Folks.

26 records · Page 2Linked to original sources

Multiple biological activities of homogeneous human alpha interferon.

To identify the active molecule in human alpha interferon preparations, we performed several studies, using both partially purified interferon and homogeneous interferon. Our results indicated that there is little difference between the partially purified and the homogeneous interferon preparations in terms of antiviral activity, inhibition of deoxyribonucleic acid synthesis in human neoplastic cells, and enhancement of human natural killer cell activity.

Cells, Cultured↗

Effect of the new immunosuppressive agent, cyclosporin-A, on natural killer cell and antibody-dependent cell-mediated cytotoxic activity.

Athymic nude mouse homozygotes (nu/nu) and the heterozygote nu/nu+ were injected intraperitoneally with 2 mg of cyclosporin-A (CS-A) twice, 72 and 1 h prior to analysis. We have found that in vivo administration of CS-A results in a significant suppression of natural killer (NK) cell and antibody-dependent cell-mediated cytotoxic (ADCC) activity which probably play an important role in tumor and graft rejection. T cells were also suppressed, in contrast, B cells were found to be immunocompetent as determined by cell proliferation and antibody-forming capacity in response to mitogens and antigens. The identity of cells mediating NK cell and ADCC activity and its relationship to T lymphocytes are also discussed.

Animals↗

Detection of human ADCC activity using automated flow cytometry.

Using automated flow cytometry techniques we have developed a rapid assay to measure human antibody-dependent cell-mediated cytotoxicity (ADCC). By staining cell cultures for DNA content, chick red blood cell targets can be readily distinguished from human effector cells and ADCC can be measured by changes in their relative proportions. The sensitivity and rapidly of the assay is shown by the finding that at an effector to target ratio of only 2:1, 42% killing can be detected after 1 h incubation.

Antibodies↗

Detection of antibody-dependent cell-mediated cytotoxicity by automated flow cytometry. Comparison to a chromium release assay and characterization of the effector cell subpopulation.

Antibody-dependent cell-mediated cytotoxicity (ADCC) against chick red blood cells (CRBC) can be detected by flow cytometric (FCM) analysis of cellular DNA content. When compared to a standard chromium release assay FCM analysis shows several advantages: (1) equivalent cytotoxicity can be detected after 1 h compared to 4 h for 51Cr; (2) equivalent cytotoxicity can be seen at a 5-fold lower effector-to-target ratio; and (3) no radiolabeling is needed. When mouse spleen cells were fractionated based on adherence to the plastic, adherent cells showed the highest ADCC by both FCM and 51Cr release.

Animals↗

Natural killer cells (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) components of Schistosoma mansoni infection.

Schistosoma mansoni cercariae were used to infect CBA-J mice, a strain characterized by possessing a high level of NK cells. 4 days after infection with cercariae, the natural cytotoxic capacity of these mice, as measured by NK and ADCC, reached a peak level of enhancement significantly greater than that of uninfected controls. Infection by this parasite appears to activate natural cell-mediated immune defense systems. Further observation of the pattern of response of NK and ADCC effector cells to infection by cercariae may reveal important information regarding the inherent immunity to the schistosome infection.

Animals↗

Interferon enhanced human natural killer and antibody-dependent cell-mediated cytotoxic activity.

Preincubation of normal human lymphocytes with human interferon for 18-24 h at 37 degrees C resulted in an increase of the activity of both natural killer (NK) cells and antibody-mediated cytotoxic cells (ADCC). The human myeloid line, K-562, which is highly susceptible to NK cells, was employed. ADCC was assessed with antibody-coated chick erythrocytes as targets. NK cells and ADCC were detected in a 4-hour 51Cr release assay. The magnitude of the enhancement was proportionate to the amount of interferon used in preincubation of the effector cells. Preincubation of tumor-target cells with interferon does not increase their susceptibility or resistance to lysis. The major effect of interferon on the cellular metabolism of the tumor-target cell is inhibition of DNA synthesis, but no direct cytotoxic effect was detected. Our findings may be important in understanding the mode of action of interferon in increasing host resistance to a variety of pathogens and tumors. This may be accomplished by inhibiting the growth of the tumor while simultaneously enhancing the natural killing mechanism for immunosurveillance.

Animals↗

Murine T-cell heterogeneity.

Immunoregulatory lymphoid cells that mature under the influence of the thymus gland (T cells) have been implicated to a major extent in the induction or at least the perpetuation of malignant neoplasms in man. Those T cells are thought to inactivate, suppress, or neutralize the normally occurring tumoricidal effector cells and thereby facilitate the unchecked growth of the neoplasm; the term "suppressor T cells" is therefore used to denote their individual activity. This concept implies that there is a balance between the effector cells and the suppressor cells in healthy subjects and that perhaps enrichment and activation of those cells involved in the defense against neoplastic growth, and specific depletion and elimination of those cells involved in suppression or inactivation of the former in patients with malignant diseases, may provide new modalities in cancer immunotherapy. Most of the studies that form the basis of this concept have been derived in animal models, particularly the mouse. The existence of cell-surface markers which have been used as phenotypic tools has provided the knowledge that distinct subpopulations of lymphoid cells do exist. The phenotypic characterization of lymphoid cells involved in functionally dinstinct immunologic events has been the object of intensive investigation. Therefore, the purpose of this paper is to briefly document our current knowledge of the functional heterogeneity that exists in murine T cells based on the differential expression of these cell-surface markers.

Animals↗

The HIV 'A' (sor) gene product is essential for virus infectivity.

The genome of the human immunodeficiency virus (HIV) contains several open reading frames (ORFs) not present in other viruses. The 'A' gene, also known as Q2 P'3, ORF-1(4) or sor5, partially overlaps the pol gene; its protein product has a relative molecular mass of 23,000 (Mr 23K) and is present in productively infected cells. The function of this protein is unclear; mutant viruses deleted in 'A' replicate in and kill CD4+ lymphocyte lines, but the high degree of conservation of the deduced amino-acid sequence in nine different HIV isolates (80%) and the presence of analogous genes in HIV-2 and other lentiviruses suggest that the gene function is an important one. Here we describe a mutant virus deficient in the 'A' gene which produces virion particles normally; however, the particles are approximately 1,000 times less infective than wild type. Transcomplementation experiments partially restore infectivity. The mutant virus spreads efficiently when virus-producing cells are co-cultivated with CD4+ lymphocytes, however, indicating that HIV can spread from cell to cell in a mechanism that does not require the 'A' gene product and probably does not require the production of infective virus particles.

Amino Acid Sequence↗