Lymphocytes expressing type 3 complement receptors proliferate in response to interleukin 2 and are the precursors of lymphokine-activated killer cells.

Gray, J. Dixon; Horwitz, David A.

doi:10.1172/jci113442

Cited by 21 publications

(12 citation statements)

References 34 publications

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“…NK cells are normally present in the circulation and, along with other populations of lymphocytes, are further activated by the T-cell lymphokine interleukin 2 (IL-2) (4)(5)(6)(7)(8)(9). These so-called lymphokine-activated killer cells, or LAK cells, display a greater lytic capacity and recognize a broader range of target cells than their nonactivated counterparts (6)(7)(8)(9). Despite these presumably capable killer cells, humans are frequently afflicted with cancer and with persistent or recurrent viral infections.…”

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confidence: 99%

Herpes simplex virus-infected cells disarm killer lymphocytes.

Confer

Vercellotti

Kotasek

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Human endothelial cells or human foreskin fibroblasts infected with herpes simplex viruses (HSVs) potently inhibit the lytic activity of natural killer cells and interleukin 2-activated killer cells. The inhibition occurs after as little as 8 hr of viral infection and requires contact between effector cells and HSV-infected targets. Inhibition evidently stems from direct blockade of killer cell function because killer cells placed atop HSV-infected targets rapidly become incapable of lysing subsequently added HL-60 or K-562 cells. The impairment of killer cell function is prevented when protein glycosylation in HSV-infected cells is blocked with tunicamycin. These studies may be relevant for understanding the persistence of herpes simplex virus infections and, further, suggest a mechanism for failed immune surveillance. A particularly relevant instance in which the immune system fails to eliminate a viral pathogen is that of human infection with herpes simplex virus (HSV). NK cells are necessary to control HSV in humans (10) but, nevertheless, fail to eradicate the infection. While investigating the role of killer lymphocytes in the recognition and elimination of HSV-infected cells, we made the unexpected observation that cytolytic activity of NK cells and LAK cells is remarkably suppressed following their contact with HSV-infected target cells. This down-regulation of cytotoxic effectors by cells infected with a common virus not only suggests a mechanism for persistence of HSV infections but also may serve as a model, in general, of failed immune surveillance. METHODSCell Culture. Human foreskin fibroblasts were cultured in tissue culture medium (RPMI-1640 with 25 mM Hepes supplemented with 2 mM L-glutamine, 100 units of penicillin per ml, and 100 ,ug of streptomycin per ml) and 10% (vol/vol) fetal bovine serum. Human umbilical vein endothelium was prepared and cultured as described (11). K-562 and HL-60 cell lines were grown in suspension culture in the same medium as above. They were passaged as necessary to maintain the density below 106 cells per ml.Virus Infection. HSV type 1 (HSV-1), strain 17 syn+, and HSV type 2 (HSV-2), strain HG52, were propagated and titrated in rabbit skin cells as described (12). Virus stock was prepared at 107 plaque-forming units (pfu)/ml of tissue culture medium with 5% calf serum and stored at -700C in small aliquots. Confluent monolayers of target cells were infected with HSV by overlaying with 100 ,ul of virus stock per well and incubating for 1 hr at 350C (multiplicity of infection 10 pfu per target cell). After the infecting incubation, the spent virus stock was removed and monolayers were overlaid with their original medium and incubated for various times before exposing them to killer cells.In experiments comparing the effects of adenovirus, strain AD4, to those of HSV, A549 cells were used as targets (13,14). Viral infection of A549 cells was carried out as above.Killer Cells. NK activity was assayed in freshly isolated peripheral blood mononuclear cells. From 60...

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mentioning

confidence: 99%

Herpes simplex virus-infected cells disarm killer lymphocytes.

Confer

Vercellotti

Kotasek

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…The molecules responsible for C3 deposition under these conditions remain unidentified. Another report has suggested that C3 deposition physiologically occurs in damaged cells for facilitating clearance by C receptor-positive leukocytes (43)(44)(45)(46). In fact, P39 + sublines were established through culture in conditions under which most cells died (18).…”

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confidence: 99%

Purification and characterization of a human membrane protein that activates the alternative complement pathway and allows the deposition of homologous complement C3.

Matsumoto

Yamashita

Iida

et al. 1995

The Journal of Experimental Medicine

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SummaryA human myeloid cell subline, P39 +, is found to be a target for human complement (C) via the alternative pathway and to allow the deposition of multiple C3 fragments on its membranes, though expressing the complement regulatory proteins decay-accelerating factor and membrane cofactor protein. The parent cell line, P39-, which is phenotypically similar to the P39 + subline, does not allow the deposition of homologous C3 fragments. In this study, we established a monoclonal antibody, M161 Ab, which reacted with P39 + but not P39-cells. This Ab recognized a 43-kD protein in P39 + cell lysate transblotted onto nitrocellulose. Using this Ab as a probe, we purified the 43-kD protein, namely, M161 antigen (Ag). M161 Ag had a basic isoelectric point (pI), 9.3-9.4 by chromatofocusing, and was precipitated as an insoluble material at the pI point. The purified M161 Ag was a single-chain protein and did not possess N-or O-linked carbohydrates. When the purified M161 Ag was transblotted onto nitrocellulose and incubated with Mg2+-EGTA serum, human C3 fragments were efficiently deposited on M161 Ag. The major species of the deposited C3 fragments was C3b. Furthermore, the C3 fragments bound to the M161 Ag were detached by 1 M hydroxylamine, suggesting that a covalent ester linkage sustains M161 Ag-C3b interaction. NH2-terminal amino acid analysis revealed that M161Ag is a novel membrane protein. Hence, it appeared that M161 Ag is a potent activator of human alternative complement pathway on human cells that activates homologous C3 and allows the deposition of C3b on itself. Thus, under some conditions, homeostasis of complement is maintained even on human cells, not only by the complement regulatory proteins, but also by membrane C3-activating molecules on which C3b is deposited.

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“…The other possibility is that VSIG4 inhibits T cell activation by acting as a complement receptor. Despite the fact that the expression of C3 receptors CR1 and CR3 on T cells was described many years ago (11)(12)(13), the function of these receptors on T cells is unclear. However, a recent study demonstrated that cross-linking CR1 and CR3 with antibodies profoundly inhibits T cell proliferation (14).…”

Section: Dual Functions Reveal More Questions Than Answersmentioning

confidence: 99%