Tags

Type your tag names separated by a space and hit enter

Dual effects of cytokines in regulation of MHC-unrestricted cell mediated cytotoxicity.
Crit Rev Immunol 1993; 13(1):1-34CR

Abstract

Natural killer (NK) cells probably function as an early defense line against viruses, due to their ability to kill virus-infected cells without resorting to clonal proliferation of memory cells. NK cells are also capable of killing tumor cells. In both cases the killing is major histocompatibility complex (MHC) unrestricted. NK cells exhibit spontaneous activity but they are positively regulated by interferon (IFN) or indirectly by such IFN-inducers as viruses, bacterial products, poly (rl):(rC), and mitogens. Interleukin-2 (IL-2) has the ability to enhance NK activity in addition to its ability to generate lymphokine-activated killer (LAK) cell activity. Recently, it was documented that other cytokines (e.g., IL-1, tumor necrosis factor (TNF), IL-6, and IL-12) are also involved in induction or enhancement of the cytotoxic activity of NK cells. Besides their "positive" regulation of NK activity, cytokines (in some cases the same cytokines) often act as "negative signals" for NK-mediated cytotoxicity. If NK susceptible target cells are exposed to IFN prior to NK cells, their sensitivity to NK activity is often markedly diminished. The mechanism by which IFNs (IFN-alpha, -beta and -gamma) affect the sensitivity of target cells to NK activity remains unknown, but it is clear that this function is not shared by other cell-mediated killing processes. The protective effect induced by IFN against NK activity is dependent on new mRNA and protein synthesis and can be abolished when target cells are incubated with combination of IFN and metabolic inhibitors or by chemotherapeutic purine or pyrimidine analogs. Class I MHC antigens have a central role in cell to cell interactions in the immune system. Because IFN has the ability to induce/increase class I MHC antigen expression, it has been suggested that class I MHC antigens act as "negative signals" of NK-mediated cytotoxicity. Although many studies support this hypothesis, others present evidence for a lack of involvement of class I MHC antigens in mediating sensitivity to NK activity. Other cytokines have been tested for their ability to affect the sensitivity of target cells to NK activity, as well as their ability to enhance the cytotoxic activity of NK effector cells. Lymphotoxin (TNF-beta) increases target cell susceptibility to NK activity. On the other hand, IL-1, IL-2, IL-6, and TNF reduce the sensitivity of target cells to NK lysis, at least in some systems.(

ABSTRACT

TRUNCATED AT 400 WORDS)

Authors+Show Affiliations

Division of Morphological Sciences, Faculty of Medicine, Israel Institute of Technology, Haifa.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

8466640

Citation

Reiter, Z. "Dual Effects of Cytokines in Regulation of MHC-unrestricted Cell Mediated Cytotoxicity." Critical Reviews in Immunology, vol. 13, no. 1, 1993, pp. 1-34.
Reiter Z. Dual effects of cytokines in regulation of MHC-unrestricted cell mediated cytotoxicity. Crit Rev Immunol. 1993;13(1):1-34.
Reiter, Z. (1993). Dual effects of cytokines in regulation of MHC-unrestricted cell mediated cytotoxicity. Critical Reviews in Immunology, 13(1), pp. 1-34.
Reiter Z. Dual Effects of Cytokines in Regulation of MHC-unrestricted Cell Mediated Cytotoxicity. Crit Rev Immunol. 1993;13(1):1-34. PubMed PMID: 8466640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual effects of cytokines in regulation of MHC-unrestricted cell mediated cytotoxicity. A1 - Reiter,Z, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - 1 EP - 34 JF - Critical reviews in immunology JO - Crit. Rev. Immunol. VL - 13 IS - 1 N2 - Natural killer (NK) cells probably function as an early defense line against viruses, due to their ability to kill virus-infected cells without resorting to clonal proliferation of memory cells. NK cells are also capable of killing tumor cells. In both cases the killing is major histocompatibility complex (MHC) unrestricted. NK cells exhibit spontaneous activity but they are positively regulated by interferon (IFN) or indirectly by such IFN-inducers as viruses, bacterial products, poly (rl):(rC), and mitogens. Interleukin-2 (IL-2) has the ability to enhance NK activity in addition to its ability to generate lymphokine-activated killer (LAK) cell activity. Recently, it was documented that other cytokines (e.g., IL-1, tumor necrosis factor (TNF), IL-6, and IL-12) are also involved in induction or enhancement of the cytotoxic activity of NK cells. Besides their "positive" regulation of NK activity, cytokines (in some cases the same cytokines) often act as "negative signals" for NK-mediated cytotoxicity. If NK susceptible target cells are exposed to IFN prior to NK cells, their sensitivity to NK activity is often markedly diminished. The mechanism by which IFNs (IFN-alpha, -beta and -gamma) affect the sensitivity of target cells to NK activity remains unknown, but it is clear that this function is not shared by other cell-mediated killing processes. The protective effect induced by IFN against NK activity is dependent on new mRNA and protein synthesis and can be abolished when target cells are incubated with combination of IFN and metabolic inhibitors or by chemotherapeutic purine or pyrimidine analogs. Class I MHC antigens have a central role in cell to cell interactions in the immune system. Because IFN has the ability to induce/increase class I MHC antigen expression, it has been suggested that class I MHC antigens act as "negative signals" of NK-mediated cytotoxicity. Although many studies support this hypothesis, others present evidence for a lack of involvement of class I MHC antigens in mediating sensitivity to NK activity. Other cytokines have been tested for their ability to affect the sensitivity of target cells to NK activity, as well as their ability to enhance the cytotoxic activity of NK effector cells. Lymphotoxin (TNF-beta) increases target cell susceptibility to NK activity. On the other hand, IL-1, IL-2, IL-6, and TNF reduce the sensitivity of target cells to NK lysis, at least in some systems.(ABSTRACT TRUNCATED AT 400 WORDS) SN - 1040-8401 UR - https://www.unboundmedicine.com/medline/citation/8466640/Dual_effects_of_cytokines_in_regulation_of_MHC_unrestricted_cell_mediated_cytotoxicity_ L2 - https://www.lens.org/lens/search?q=citation_id:8466640 DB - PRIME DP - Unbound Medicine ER -