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Biomedical subjects

M Malkovsky

Publications and source records attributed to M Malkovsky.

65 records · Page 4Linked to original sources
PubMed1985

In vivo activity of interleukin-2: conversion of a stimulus causing unresponsiveness to a stimulus causing contact hypersensitivity by the injection of interleukin-2.

The intravenous injection of hapten-modified (picrylated) cells causes unresponsiveness. When conventional or recombinant interleukin-2 (IL-2) is also injected, strong contact sensitivity occurs. This IL-2 is effective when given 7 hr after the injection of the picrylated cells or 2 days later, but has no effect when given beforehand. It is suggested that picrylated cells given intravenously fail to induce contact sensitivity secondary to a failure of IL-2 production, and that IL-2 may be one of the second signals which converts a 'tolerogenic' stimulus into an immunogenic stimulus.

Animals↗
PubMed1984

The role of B cell differentiation factors and specific T cell help in the pathogenesis of primary hypogammaglobulinemia.

We have examined the function of T and B cells from patients with late onset primary acquired hypogammaglobulinemia (PHG). T cells from these patients give effective help to normal B cells for antigen-dependent antibody synthesis. PHG mononuclear cells also synthesize normal quantities of B cell differentiation factors, which enhance IgG, IgM and antigen-dependent antibody synthesis by normal lymphocytes. While patient T cells appear to behave appropriately, the responsiveness of patient B cells is abnormal. Although they respond to differentiation factors with increased synthesis of IgM, overall levels are 10-50-fold lower than normal B cells, and they produce little or no IgG. This pattern of response is not altered if normal T cells are the source of help. The poor response of the B cell appears to represent immaturity rather than an inherent defect, as IgG-secreting clones can be obtained after Epstein-Barr virus transformation of lymphocytes from certain patients, and some of these clones respond to differentiation factors with increased IgG production. The lack of any functional defect in the T population, and the apparent immaturity rather than abnormality of the B cells, may implicate accessory cells in the pathogenesis of the disease.

Agammaglobulinemia↗
PubMed1984

T helper factor in contact sensitivity: antigen-specific I-A+ helper factor is made by an Lyt-1+2-, I-A+, I-J- T cell.

Antigen-specific T helper factor appears in the 24 hr supernatant of lymph node cells taken 4 days after immunization with contact sensitizer. The factor is assayed by its ability to augment the contact sensitivity response induced by haptenized spleen cells. In practice, picrylated or oxazolonated spleen cells are treated with the factor for 1 hr at 4 degrees and 4 x 10(6) cells are injected into the footpads of recipient mice. Contact sensitivity is assessed 5 days later. The factor first appears 3 days after immunization and its production depends on an Lyt-1+2-, I-A+, I-J- T cell. It is antigen-specific in its action in a criss-cross experiment, and can be absorbed with and eluted from haptenized beads. It bears I-A determinant(s) and the I-A determinant and the antigen binding site(s) occur on the same molecule. The molecular weight is around 60,000. The possible role of T helper factors in the activation of the antigen-presenting cell in the induction stage of the immune response is discussed.

Animals↗
PubMed1984

Suppressor cells induced by BCG release non-specific factors in vitro which inhibit DNA synthesis and interleukin-2 production.

Mice injected intravenously with a high dose (5 X 10(7) ) of BCG fail to develop delayed hypersensitivity to BCG and are described as anergic or unresponsive. Spleen cells from these mice release factors on culture which suppress DNA synthesis induced by concanavalin A in vitro. Cell separation experiments showed that both macrophages and T cells produce inhibitory factors. However, the macrophage factor has a molecular weight 10,000-30,000, while the T cell factor has a molecular weight of 50,000-70,000. Further evidence that these two factors are different is provided by the kinetics of their action. The T cell factor only acts when given within 12 hr of stimulation with concanavalin A, while the macrophage factor acts even when given at 48 hr. In the case of the T cell factor, the inhibition of DNA synthesis may be attributed to its ability to block the interleukin-2 production induced by Con A. As similar T cell and macrophage factors are produced in mice responding to simple chemically reactive haptenes (contact sensitizers), it is possible that a similar suppressor circuit is involved in the control of the response to contact sensitizers and in the production of unresponsiveness (anergy) in mice given large doses of BCG.

Animals↗
PubMedDate not supplied

Cellular immune responses in rhesus macaques infected rectally with low dose simian immunodeficiency virus.

Monkeys infected rectally with low dose simian immunodeficiency virus (SIV) were resistant to high dose challenge with SIV. Peripheral blood mononuclear cells (PBMC) from two of four challenged monkeys were unable to support SIV replication in vitro unless cultures were depleted of CD8+ lymphocytes. Monkeys that had survived high dose rectal infection with SIV also suppressed virus replication in cultured PBMC. PBMC from uninfected monkeys supported virus replication in both unfractionated and CD8-depleted cultures. Virus-suppressive activity of PBMC may be an important correlate of protective immunity in AIDS.

Animals↗
PubMedDate not supplied

Antiviral activity of primate gamma delta T lymphocytes isolated by magnetic cell sorting.

The exposure of human or rhesus monkey peripheral blood mononuclear cells (PBMCs) to interleukin 2 (IL-2) in vitro resulted in a selective outgrowth of gamma delta lymphocytes. Using positive selection by monoclonal antibodies and magnetic beads, gamma delta T lymphocytes were isolated from these cultures. Without priming by viral antigens, the purified gamma delta T lymphocytes lyse immunodeficiency virus-infected cells substantially better than the uninfected counterparts.

Animals↗
PubMedDate not supplied

An Hsp60 related protein is associated with purified HIV and SIV.

The possible physical association of heat shock proteins (Hsp's) with immunodeficiency viruses (HIV and SIV) has been examined. The virions were purified by a) polyethylene glycol (PEG) precipitation and Sepharose 4B filtration, b) PEG precipitation and centrifugation over a Renografin gradient, or c) PEG precipitation and Matrex Cellufine Sulfate affinity chromatography. Western blotting revealed an Hsp60 related protein associated with HIV and SIV. Other Hsp's (such as Hsp70) were not detected, suggesting a specific interaction between Hsp60 and viral factors.

Antibodies, Monoclonal↗
PubMedDate not supplied

Fas-dependent, activation-induced cell death of gammadelta cells.

Activated gammadelta T cells undergo apoptosis upon restimulation of their T cell receptor (TCR)/CD3 complex. We demonstrate that in these cells, the activation-induced cell death (AICD) is mediated by Fas and Fas ligand (FasL) interaction. The activated gammadelta T cells are prone to AICD initiated by exposure to mitogens, anti-TCR/CD3 antibodies, as well as specific antigens such as Daudi cells or ethylpyrophosphate (Etpp). Cells that have been activated twice, and consequently more susceptible to AICD than primary cells, display augmented tyrosine phosphorylation in comparison with control cells. These studies outline a mechanism that may regulate gammadelta T cell activities in immune responses and limit the expansion of activated T cells repeatedly exposed to antigens.

Apoptosis↗
PubMedDate not supplied

Are gamma delta T cells important for the elimination of virus-infected cells?

Rhesus monkeys (Macaca mulatta) gamma delta T cells were identified using a monoclonal antibody. The relative representation of gamma delta T lymphocytes in the peripheral blood, lymph nodes, and spleen resembles that of Homo sapiens. The analysis of function and specificity revealed further significant similarities between the simian and human gamma delta T-cell systems. Since both human and monkey gamma delta T lymphocytes can effectively lyse cells infected with immunodeficiency viruses, it is possible that the primate gamma delta T-cell systems contribute to antiviral immunosurveillance.

Animals↗
PubMedDate not supplied

Pathogenesis of SIVmac251 after atraumatic inoculation of the rectal mucosa in rhesus monkeys.

Intrarectal inoculation of rhesus monkeys with low doses of SIVmac led to a prolonged clinical and virological latency that was not observed for high intrarectal doses or for intravenous inoculation. Animals infected intrarectally with low virus doses remained negative for serum antibody responses to SIV for at least one year even though they readily transferred SIV to naive recipients via transfusion of whole blood.

Animals↗