Nonspecific inhibitor released by T acceptor cells reduces the production of interleukin-2.
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Biomedical subjects
Publications and source records attributed to M Malkovsky.
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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.
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.
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.
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.
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.