Natural killer susceptibility of human cells may be regulated by genes in the HLA region on chromosome 6.

“…The Daudi cell line is deficient for HLA class I antigens due to defective (32m synthesis but expresses HLA class II antigens, while Raji expresses both HLA class I and II . Although-non-MHC-restricted lysis appears to correlate inversely with the expression of HLA class I antigens on some target cells (20,21), this does The clones were derived from a culture of PBL primed to the LCL TK6 for 7 d followed by FACS sorting for TCR-y/b' cells . Clones were screened for cytotoxicity on the indicated target cell lines .…”

Section: Resultsmentioning

confidence: 99%

Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

Fisch

Malkovsky

Braakman

et al. 1990

The Journal of Experimental Medicine

159

View full text Add to dashboard Cite

Non-MHC-restricted killer cells are cytotoxic lymphocytes that can mediate cytolysis of most tumor targets without apparent selectivity and restriction by the MHC, particularly when activated with IL-2. These effector cells include predominantly NK cells and T cells expressing the TCR-gamma/delta. We found that TCR-gamma/delta-1+, delta TSC1-, BB3+, Ti gamma A+ T cell clones mediate a characteristic cytolytic pattern of non-MHC-restricted cytolysis that is markedly different from NK clones and alpha/beta T cell clones derived from the peripheral blood of the same normal individuals. The characteristic finding is that all BB3/Ti gamma A+ gamma/delta clones mediate strong cytolysis of Daudi cells but they do not lyse Raji cells. In contrast, NK clones from the same donors mediate strong cytolysis of both Daudi and Raji targets. Cytotoxicity by the gamma/delta clones on certain target cells such as Daudi and Molt 4 can be specifically inhibited by mAbs reactive against the TCR-gamma/delta. Therefore, the TCR-gamma/delta on these clones either directly recognizes target epitopes on some tumor targets or it is involved in the regulation of their cytotoxic function. The expression of TCR-gamma/delta products reacting with the BB3 and Ti gamma A mAbs reflects the usage of identical TCR-gamma/delta V region genes that appear to be associated with the characteristic pattern of non-MHC-restricted cytotoxicity displayed by this major subset of human peripheral blood gamma/delta cells.

show abstract

“…It is also worth mentioning that IFN-is one of the cytokines released by LAK effectors [29] and has been demonstrated to be a growth factor for pulmonary fibroblasts [31]. The mechanisms responsible for target cell resistance to lysis are in part related to the up-regulation of MHC class I, class II antigens [32,33] and CD54 antigen (data not shown).…”

mentioning

confidence: 99%

Lysis of pulmonary fibroblasts by lymphokine (IL-2)-activated killer cells—a mechanism affecting the human lung microenvironment?

Zambello

Trentin

Enthammer

et al. 1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYIn this study we investigated whether IL-2-activated killer cells may bind and exert lytic activity against non-transformed lung fibroblasts. We demonstrated that human lymphokine-activated killer (LAK) cells generated in vitro following incubation with recombinant IL-2 of either peripheral blood mononuclear cells (PB-LAK) or lymphocytes obtained from bronchoalveolar lavage (BAL-LAK), but not resting cells, can lyse normal lung fibroblasts obtained from transbronchial lung biopsies in a 4-h 51 Cr release assay. Both autologous and allogeneic fibroblasts were consistently lysed by LAK cells, thus suggesting that the phenomenon we observed is not MHC-restricted. Since fibroblasts can bind IL-2 through specific receptors, we evaluated whether long-term culture with rIL-2 could modulate the susceptibility to lysis of target cells. Our data showed that autologous fibroblasts were more resistant to lysis than allogeneic fibroblasts when they were cultured with rIL-2. Since LAK cells have been demonstrated to release a series of different immunomodulatory cytokines, we evaluated the effect of short-term incubation of fibroblasts with different factors, including IL-1, IL-2, IL-3, IL-4, IL-6, tumour necrosis factor-alpha (TNF-®), and interferon-gamma (IFN-°), on the binding and the lysis mediated by LAK cells. These cytokines were not directly cytotoxic on fibroblasts. Only IFN-°was found to have a significant protective effect against the lysis. Our data support the concept that a self-directed cytotoxicity against pulmonary fibroblasts is generated during lymphocyte activation with rIL-2.

show abstract

Natural killer susceptibility of human cells may be regulated by genes in the HLA region on chromosome 6.

Cited by 120 publications

References 25 publications

Recombinant gamma interferon provokes resistance of human breast cancer cells to spontaneous and IL-2 activated non-MHC restricted cytotoxicity

Recombinant gamma interferon provokes resistance of human breast cancer cells to spontaneous and IL-2 activated non-MHC restricted cytotoxicity

Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis.

Lysis of pulmonary fibroblasts by lymphokine (IL-2)-activated killer cells—a mechanism affecting the human lung microenvironment?

Contact Info

Product

Resources

About