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Biomedical subjects

T Folks

Publications and source records attributed to T Folks.

7 recordsLinked to original sources

A monocyte-derived factor interferes with detection of reverse transcriptase in HIV-1 infection.

Culture supernatants from the rabbit macrophage cell line 6083 infected with a retrovirus, human immunodeficiency virus type 1 (HIV-1), were negative for reverse transcriptase (RT) expression although the line was shown to be productively infected by all other criteria tested. Supernatants from uninfected cultures of 6083, the human monocyte line U937, and from freshly isolated peripheral human monocytes, were found to contain a monocyte-derived inhibitory factor (MDIF) which interferes with a standard assay for RT. MDIF is a heat-labile activity of approximately of 40 kD. Both substrates and products of the reverse transcriptase assay are degraded by MDIF which is not affected by reduction and alkylation of disulfide bonds. MDIF is inhibited by the addition of a particular thioated oligonucleotide (S-dG30) to the reaction mixture but this addition also inhibits RT. The optimum method to minimize MDIF interference in the RT assay is by addition of ethylene glycol bis-(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA); MDIF requires divalent cations for activity and has a strong preference for calcium which is preferentially chelated by EGTA. The potential presence of this inhibitory activity should be considered when using RT levels as a measure of retroviral infection.

Animals

Infection of rabbits with human immunodeficiency virus 1. A small animal model for acquired immunodeficiency syndrome.

Injection of rabbits with a human T cell line infected with HIV-1 caused seroconversion within 6 wk, and HIV-1 could be isolated from PBL cultures of infected rabbits. Identity of the isolated virus with HIV-1 was shown by analysis of products amplified by the polymerase chain reaction. HIV-1 infection was seen in rabbits injected with HIV-1-infected cells alone as well as in those that were first infected with HTLV-1 and subsequently with HIV-1. There were no consistent signs of disease in the rabbits infected with HIV-1 alone but HTLV-1/HIV-1-infected rabbits showed signs of illness including diarrhea and weight loss, transient neurologic impairment and, in one animal, a rapidly progressing mammary adenocarcinoma. Examination of organs taken at necropsy from both HIV-1- and HTLV-1/HIV-1-infected animals showed splenic hyperplasia and lymphocyte infiltration of the lungs, as well as moderate damage to liver and kidney in some cases.

Acquired Immunodeficiency Syndrome

Susceptibility of normal human lymphocytes to infection with HTLV-III/LAV.

Normal human peripheral blood lymphocytes were tested for their susceptibility to infection with retroviruses isolated from patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Of 10 normal individuals tested, lymphocytes from all subjects became infected and produced virus as detected by assay for Mg+2-dependent reverse transcriptase. Lymphocytes from different individuals were demonstrated to be either high or low producers of reverse transcriptase after infection. The kinetics of virus production were similar in cells from both high- and low-producing individuals. A significant correlation was observed between high and low viral-producing lymphocytes and expression of the Leu-3/T4 (CD4) surface molecule. Mitogen-stimulated peripheral blood lymphocytes exposed to HTLV-III/LAV manifested productive viral infection, as reflected by the appearance of early syncytia, followed by reverse transcriptase. Unstimulated peripheral blood lymphocyte cultures displayed late syncytia but no detectable reverse transcriptase upon exposure to virus. The addition of anti-human interferon-alpha did not appear to have an appreciable effect on viral production in normal peripheral blood lymphocytes exposed to the virus.

Acquired Immunodeficiency Syndrome

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