immunologic cytotoxicity


Summary: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.

Top Publications

  1. Lassen M, Lukens J, Dolina J, Brown M, Hahn Y. Intrahepatic IL-10 maintains NKG2A+Ly49- liver NK cells in a functionally hyporesponsive state. J Immunol. 2010;184:2693-701 pubmed publisher
  2. Ferch U, Kloo B, Gewies A, Pfänder V, Duwel M, Peschel C, et al. Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells. J Exp Med. 2009;206:2313-20 pubmed publisher
    ..Thus, our results indicate a growth-promoting role for MALT1 paracaspase activity in ABC-DLBCL and suggest that a pharmacological MALT1 protease inhibition could be a promising approach for lymphoma treatment. ..
  3. Beal A, Anikeeva N, Varma R, Cameron T, Vasiliver Shamis G, Norris P, et al. Kinetics of early T cell receptor signaling regulate the pathway of lytic granule delivery to the secretory domain. Immunity. 2009;31:632-42 pubmed publisher
    ..The short pathway is associated with faster granule release and more efficient killing than the long pathway. Thus, the kinetics of early signaling regulates the quality of the T cell cytolytic response...
  4. Jenkins M, Tsun A, Stinchcombe J, Griffiths G. The strength of T cell receptor signal controls the polarization of cytotoxic machinery to the immunological synapse. Immunity. 2009;31:621-31 pubmed publisher
    ..By controlling centrosome and granule polarization independently, the centrosome is able to respond rapidly to weak signals so that CTLs are poised and ready for the trigger for granule delivery. ..
  5. Rosenblatt J, Wu Z, Vasir B, Zarwan C, Stone R, Mills H, et al. Generation of tumor-specific T lymphocytes using dendritic cell/tumor fusions and anti-CD3/CD28. J Immunother. 2010;33:155-66 pubmed publisher
    ..These findings indicate that stimulation with DC/tumor fusions provides a unique platform for subsequent expansion with anti-CD3/CD28 in adoptive T-cell therapy of cancer. ..
  6. Guo H, Kumar P, Moran T, Garcia Sastre A, Zhou Y, Malarkannan S. The functional impairment of natural killer cells during influenza virus infection. Immunol Cell Biol. 2009;87:579-89 pubmed publisher
    ..Our observations show the presence of a new, but yet to be explored, mechanism by which the influenza virus can evade immune detection. ..
  7. Liu D, Bryceson Y, Meckel T, Vasiliver Shamis G, Dustin M, Long E. Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses. Immunity. 2009;31:99-109 pubmed publisher
    ..Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling. ..
  8. Bangham C. CTL quality and the control of human retroviral infections. Eur J Immunol. 2009;39:1700-12 pubmed publisher
    ..e. in the frequency, phenotype and function or quality of T cells, are the causes or effects - or both - of the variation in the efficiency of virus control...
  9. Suzuki D, Tsuji K, Yamamoto T, Fujii K, Iwatsuki K. Production of proinflammatory cytokines without invocation of cytotoxic effects by an Epstein-Barr virus-infected natural killer cell line established from a patient with hypersensitivity to mosquito bites. Exp Hematol. 2010;38:933-44 pubmed publisher

More Information


  1. Chargui J, Combaret V, Scaglione V, Iacono I, Peri V, Valteau Couanet D, et al. Bromohydrin pyrophosphate-stimulated Vgamma9delta2 T cells expanded ex vivo from patients with poor-prognosis neuroblastoma lyse autologous primary tumor cells. J Immunother. 2010;33:591-8 pubmed publisher
  2. ten Brinke A, van Schijndel G, Visser R, de Gruijl T, Zwaginga J, Van Ham S. Monophosphoryl lipid A plus IFNgamma maturation of dendritic cells induces antigen-specific CD8+ cytotoxic T cells with high cytolytic potential. Cancer Immunol Immunother. 2010;59:1185-95 pubmed publisher
    ..Furthermore, the CTLs proved to kill tumour cells expressing endogenous tumour antigen in vitro. Therefore, MPLA/IFNgamma DCs are very promising for the use in future cancer immunotherapy. ..
  3. Champsaur M, Lanier L. Effect of NKG2D ligand expression on host immune responses. Immunol Rev. 2010;235:267-85 pubmed publisher
    ..We also discuss the host response to both membrane-bound and secreted NKG2D ligands and summarize the models proposed to explain the consequences of this differential expression. ..
  4. Dong H, Rowland I, Tuohy K, Thomas L, Yaqoob P. Selective effects of Lactobacillus casei Shirota on T cell activation, natural killer cell activity and cytokine production. Clin Exp Immunol. 2010;161:378-88 pubmed publisher
    ..LcS also induced both proinflammatory and anti-inflammatory cytokine production in the absence of LPS, but in some cases inhibited LPS-induced cytokine production. Monocytes play an important role in LcS-induced immunological responses. ..
  5. Tamura T, Fukutomi Y, Makino M. [Forefront of vaccine development: tuberculosis and leprosy]. Nihon Hansenbyo Gakkai Zasshi. 2009;78:271-6 pubmed
    ..These results suggest that Th1 immune response induced by Peptide-25 plays an important role in the induction of functional activation of CD8+ cytotoxic T cells. ..
  6. Verneris M, Miller J. The phenotypic and functional characteristics of umbilical cord blood and peripheral blood natural killer cells. Br J Haematol. 2009;147:185-91 pubmed publisher
    ..Activation and expansion protocols for UCB NK cells are briefly reviewed. Lastly, we outline the early use of UCB NK cells in clinical trials. ..
  7. Stannard K, Collins P, Ito K, Sullivan E, Scott S, Gabutero E, et al. Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model. Cancer Lett. 2010;299:95-110 pubmed publisher
    ..This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo. ..
  8. Taniguchi M, Tashiro T, Dashtsoodol N, Hongo N, Watarai H. The specialized iNKT cell system recognizes glycolipid antigens and bridges the innate and acquired immune systems with potential applications for cancer therapy. Int Immunol. 2010;22:1-6 pubmed publisher
    ..On the basis of these mechanisms, iNKT cell-targeted adjuvant cell therapies have been developed and have shown great promise in initial clinical trials on cancer patients. ..
  9. Dressel R, Nolte J, Elsner L, Novota P, Guan K, Streckfuss Bömeke K, et al. Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells. FASEB J. 2010;24:2164-77 pubmed publisher
  10. Xie X, Stadnisky M, Coats E, Ahmed Rahim M, Lundgren A, Xu W, et al. MHC class I D(k) expression in hematopoietic and nonhematopoietic cells confers natural killer cell resistance to murine cytomegalovirus. Proc Natl Acad Sci U S A. 2010;107:8754-9 pubmed publisher
    ..Thus, MHC-I D(k) is the H-2(k)-linked Cmv(r) locus; these findings suggest a role for NK cell interaction with D(k)-bearing hematopoietic and nonhematopoietic cells to shape NK-mediated virus immunity. ..
  11. Lindorfer M, Pawluczkowycz A, Peek E, Hickman K, Taylor R, Parker C. A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement. Blood. 2010;115:2283-91 pubmed publisher
    ..These findings suggest an approach to PNH treatment in which both intravascular and extravascular hemolysis can be inhibited while preserving important immune functions of the classical pathway of complement. ..
  12. Chelius D, Ruf P, Gruber P, Plöscher M, Liedtke R, Gansberger E, et al. Structural and functional characterization of the trifunctional antibody catumaxomab. MAbs. 2010;2:309-19 pubmed
    ..Binding measurement revealed the unique trifunctional features of catumaxomab. Other analytical tools were used to evaluate characteristics of catumaxomab preparations, including the presence of isoforms and aggregates. ..
  13. York N, Mendoza J, Ortega S, Benagh A, Tyler A, Firan M, et al. Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis. J Autoimmun. 2010;35:33-44 pubmed publisher
    ..Our studies reveal a novel and unexpected immune regulatory function for neuroantigen-specific CD8+T cells and have interesting biologic and therapeutic implications. ..
  14. Takeuchi M, Inoue T, Otani T, Yamasaki F, Nakamura S, Kibata M. Cell-in-cell structures formed between human cancer cell lines and the cytotoxic regulatory T-cell line HOZOT. J Mol Cell Biol. 2010;2:139-51 pubmed publisher
    ..Furthermore, we propose that cell-in-cell structures between HOZOT cells and target cancer cells could be one of the cytotoxic mechanisms of HOZOT cells. ..
  15. Jahrsdorfer B, Vollmer A, Blackwell S, Maier J, Sontheimer K, Beyer T, et al. Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion. Blood. 2010;115:1156-65 pubmed publisher
    ..Our results provide novel information about the complex network of pDC-T-cell interactions and may contribute to an improvement of prophylactic and therapeutic vaccinations. ..
  16. von Lilienfeld Toal M, Frank S, Leyendecker C, Feyler S, Jarmin S, Morgan R, et al. Reduced immune effector cell NKG2D expression and increased levels of soluble NKG2D ligands in multiple myeloma may not be causally linked. Cancer Immunol Immunother. 2010;59:829-39 pubmed publisher
    ..These results indicate that MM is associated with a significant reduction in NKG2D expression which may be contact-mediated rather than caused by soluble NKG2D ligands. ..
  17. Strell C, Sievers A, Bastian P, Lang K, Niggemann B, Zanker K, et al. Divergent effects of norepinephrine, dopamine and substance P on the activation, differentiation and effector functions of human cytotoxic T lymphocytes. BMC Immunol. 2009;10:62 pubmed publisher
    ..Therefore, we investigated the influence of norepinephrine, dopamine and substance P on the key tasks of CD8+ T lymphocytes: activation, migration, extravasation and cytotoxicity...
  18. Berthon C, Driss V, Liu J, Kuranda K, Leleu X, Jouy N, et al. In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors. Cancer Immunol Immunother. 2010;59:1839-49 pubmed publisher
    ..The efficacy of MEK inhibitors against B7-H1-mediated inhibition of CTLs suggests a possible cancer immunotherapy strategy using targeted drugs. ..
  19. Ashton Rickardt P. Serine protease inhibitors and cytotoxic T lymphocytes. Immunol Rev. 2010;235:147-58 pubmed publisher
  20. Bovenschen N, Kummer J. Orphan granzymes find a home. Immunol Rev. 2010;235:117-27 pubmed publisher
    ..In this review, we summarize and discuss what is currently known about the biology of the human orphan granzymes. ..
  21. Benson V, Grobarova V, Richter J, Fiserova A. Glycosylation regulates NK cell-mediated effector function through PI3K pathway. Int Immunol. 2010;22:167-77 pubmed publisher
    ..In conclusion, the modulation of glycosyltransferases MGAT3 and MGAT5 by synthetic GN4C correlated with the improvement of NK cell effector functions and the augmentation of tumor cells sensitivity to NK cell-mediated cytotoxicity. ..
  22. de Goër de Herve M, Dembele B, Vallée M, Herr F, Cariou A, Taoufik Y. Direct CD4 help provision following interaction of memory CD4 and CD8 T cells with distinct antigen-presenting dendritic cells. J Immunol. 2010;185:1028-36 pubmed publisher
    ..CD4 help for memory CD8 T cells therefore appears to be conditioned primarily not by Ag specificity but by activation status...
  23. Moriya K, Wakabayashi A, Shimizu M, Tamura H, Dan K, Takahashi H. Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205(+) dendritic cells. Cancer Immunol Immunother. 2010;59:1083-95 pubmed publisher
  24. Wang K, Zhou Q, Guo A, Xu C, An S, Wu Y. An autologous therapeutic dendritic cell vaccine transfected with total lung carcinoma RNA stimulates cytotoxic T lymphocyte responses against non-small cell lung cancer. Immunol Invest. 2009;38:665-80 pubmed
    ..Immature DCs transfected with total lung carcinoma RNA by electroporation in vitro effectively stimulate antigen-specific CTL responses against tumor cells. ..
  25. Sakly N, Boumiza R, Zrour Hassen S, Hamzaoui A, Ben Yahia S, Amara H, et al. HLA-B27 and HLA-B51 determination in Tunisian healthy subjects and patients with suspected ankylosing spondylitis and Behçet's disease. Ann N Y Acad Sci. 2009;1173:564-9 pubmed publisher
    ..This highlights the usefulness of HLA-B27, rather than that of HLA-B51, in the diagnosis of the respective diseases...
  26. Shaha S, Tomic J, Shi Y, Pham T, Mero P, White D, et al. Prolonging microtubule dysruption enhances the immunogenicity of chronic lymphocytic leukaemia cells. Clin Exp Immunol. 2009;158:186-98 pubmed publisher
    ..Use of PKC agonists and microtubule inhibitors to mimic TLR-signalling, and increase the immunogenicity of CLL cells, has implications for the design of chemo-immunotherapeutic strategies. ..
  27. Bosco A, Ehteshami S, Stern D, Martinez F. Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction. Mucosal Immunol. 2010;3:399-409 pubmed publisher
    ..Our findings show that decreased activation of Th1-like/cytotoxic and interferon pathways is a hallmark of acute exacerbation responses in asthmatic children with evidence of chronic airways obstruction. ..
  28. Ciesielski M, Ahluwalia M, Munich S, Orton M, Barone T, Chanan Khan A, et al. Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. Cancer Immunol Immunother. 2010;59:1211-21 pubmed publisher
    ..Thus, SVN53-67/M57 may act as a peptide mimic to induce an enhanced antitumor CTL response in tumor patients. The use of SVN53-67/M57 as a cancer vaccine might have application for cancer vaccine therapy. ..
  29. Kobori H, Hashiguchi M, Piao J, Kato M, Ritprajak P, Azuma M. Enhancement of effector CD8+ T-cell function by tumour-associated B7-H3 and modulation of its counter-receptor triggering receptor expressed on myeloid cell-like transcript 2 at tumour sites. Immunology. 2010;130:363-73 pubmed publisher
    ..Our results suggest that tumour-associated B7-H3 directly augments CD8(+) T-cell effector function, possibly by ligation of TLT-2 on tumour-infiltrating CD8(+) T cells at the local tumour site. ..
  30. Li P, Burke S, Wang J, Chen X, Ortiz M, Lee S, et al. Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science. 2010;329:85-9 pubmed publisher
    ..Therefore, ITNKs may represent a new cell source for cell-based therapies. ..
  31. Höglund P, Brodin P. Current perspectives of natural killer cell education by MHC class I molecules. Nat Rev Immunol. 2010;10:724-34 pubmed publisher
  32. Brenner C, King S, Przewoznik M, Wolters I, Adam C, Bornkamm G, et al. Requirements for control of B-cell lymphoma by NK cells. Eur J Immunol. 2010;40:494-504 pubmed publisher
    ..Thus, NK-receptor coengagement is crucial for NK-cell functions in vivo and especially for NK cell-mediated tumor surveillance. ..
  33. de Vries R, Yüksel S, Osterhaus A, De Swart R. Specific CD8(+) T-lymphocytes control dissemination of measles virus. Eur J Immunol. 2010;40:388-95 pubmed publisher
    ..In conclusion, we have developed a powerful tool to study cellular immunity against measles, and demonstrate that control of MV dissemination is mediated by virus-specific CD8(+) rather than by CD4(+) T-lymphocytes...
  34. Gorczynski R, Chen Z, Diao J, Khatri I, Wong K, Yu K, et al. Breast cancer cell CD200 expression regulates immune response to EMT6 tumor cells in mice. Breast Cancer Res Treat. 2010;123:405-15 pubmed publisher
    ..Finally, we report that tumor growth in vivo can be monitored by levels of soluble CD200 (sCD200) in serum of tumor-bearing animals. ..
  35. Frank A, Zhang X, Katsounas A, Bharucha J, Kottilil S, Imamichi T. Interleukin-27, an anti-HIV-1 cytokine, inhibits replication of hepatitis C virus. J Interferon Cytokine Res. 2010;30:427-31 pubmed publisher
    ..IL-27 induces STAT-1 and -3 in the cell line, and dose-dependently inhibited HCV. These data suggest that IL-27 may play a role in the development of a novel immunotherapeutic strategy for HCV and HCV/HIV co-infection. ..
  36. Nishihori Y, Kato K, Tanaka M, Okamoto T, Hagiwara S, Araki N, et al. Interleukin-2 gene transfer potentiates the alpha-galactosylceramide-stimulated antitumor effect by the induction of TRAIL in NKT and NK cells in mouse models of subcutaneous and metastatic carcinoma. Cancer Biol Ther. 2009;8:1763-70 pubmed
    ..This study shows the efficacy of alpha-GalCer/AdmIL-2 immunomodulatory therapy, and provides a cellular mechanism on how it exerts the antitumor effects. ..
  37. Stegmann K, Björkström N, Veber H, Ciesek S, Riese P, Wiegand J, et al. Interferon-alpha-induced TRAIL on natural killer cells is associated with control of hepatitis C virus infection. Gastroenterology. 2010;138:1885-97 pubmed publisher
    ..Natural killer (NK) cells might be associated with control of HCV infection. We examined the effects of IFNalpha on human NK cells and its relevance to HCV infection...
  38. Farrand K, Dickgreber N, Stoitzner P, Ronchese F, Petersen T, Hermans I. Langerin+ CD8alpha+ dendritic cells are critical for cross-priming and IL-12 production in response to systemic antigens. J Immunol. 2009;183:7732-42 pubmed publisher
    ..These data suggest a critical role for the langerin(+) compartment of the CD8alpha(+) DC population in cross-priming and IL-12 production. ..
  39. Vucic D, Dixit V. Masking MALT1: the paracaspase's potential for cancer therapy. J Exp Med. 2009;206:2309-12 pubmed publisher
    ..New data shows that targeting MALT1 protease activity may be a promising therapeutic strategy for treating aggressive B cell lymphomas. ..
  40. Yagel S. The developmental role of natural killer cells at the fetal-maternal interface. Am J Obstet Gynecol. 2009;201:344-50 pubmed publisher
  41. Szkaradkiewicz A, Karpiński T, Drews M, Borejsza Wysocki M, Majewski P, Andrzejewska E. Natural killer cell cytotoxicity and immunosuppressive cytokines (IL-10, TGF-beta1) in patients with gastric cancer. J Biomed Biotechnol. 2010;2010:901564 pubmed publisher
    ..Gastric carcinoma cells may release IL-10, the suppressive activity of which may in a secondary manner decrease NK cytotoxicity. ..
  42. Loser K, Brzoska T, Oji V, Auriemma M, Voskort M, Kupas V, et al. The neuropeptide alpha-melanocyte-stimulating hormone is critically involved in the development of cytotoxic CD8+ T cells in mice and humans. PLoS ONE. 2010;5:e8958 pubmed publisher
    ..Therefore, treatment of contact allergies or skin cancer with alpha-melanocyte-stimulating hormone or other more stable agonists of melanocortin-1 receptor might ameliorate disease or improve antitumoral immune responses. ..
  43. Godal R, Bachanova V, Gleason M, McCullar V, Yun G, Cooley S, et al. Natural killer cell killing of acute myelogenous leukemia and acute lymphoblastic leukemia blasts by killer cell immunoglobulin-like receptor-negative natural killer cells after NKG2A and LIR-1 blockade. Biol Blood Marrow Transplant. 2010;16:612-21 pubmed publisher
    ..Thus strategies to interrupt NKG2A and LIR-1 in combination with anti-KIR blockade hold promise for exploiting NK cell therapy in acute leukemias. ..
  44. Pegram H, Haynes N, Smyth M, Kershaw M, Darcy P. Characterizing the anti-tumor function of adoptively transferred NK cells in vivo. Cancer Immunol Immunother. 2010;59:1235-46 pubmed publisher
    ..Overall, the results of this study have important implications for enhancing NK cell-based immunotherapies. ..
  45. Lindgren A, Yun C, Lundgren A, Sjoling A, Ohman L, Svennerholm A, et al. CD8- natural killer cells are greatly enriched in the human gastrointestinal tract and have the capacity to respond to bacteria. J Innate Immun. 2010;2:294-302 pubmed publisher
    ..These findings may have important implications for the understanding of NK cell subsets and the innate defense against gastrointestinal bacterial infections...
  46. Zhuo M, Fujiki M, Wang M, Piard Ruster K, Wai L, Wei L, et al. Identification of the rat NKG2D ligands, RAE1L and RRLT, and their role in allograft rejection. Eur J Immunol. 2010;40:1748-57 pubmed publisher
    ..In conclusion, our results suggest that expression of NKG2D ligands may be important in allograft rejection. ..
  47. Adams C, Housley W, Bhowmick S, Cone R, Rajan T, Forouhar F, et al. Cbl-b(-/-) T cells demonstrate in vivo resistance to regulatory T cells but a context-dependent resistance to TGF-beta. J Immunol. 2010;185:2051-8 pubmed publisher
  48. Das A, Long E. Lytic granule polarization, rather than degranulation, is the preferred target of inhibitory receptors in NK cells. J Immunol. 2010;185:4698-704 pubmed publisher
    ..Therefore, granule polarization, rather than degranulation, is the preferred target of inhibitory receptors in NK cells. ..
  49. Blackburn S, Crawford A, Shin H, Polley A, Freeman G, Wherry E. Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion. J Virol. 2010;84:2078-89 pubmed publisher
    ..These observations have implications for human chronic infections and for therapeutic interventions based on blockade of the PD-1 pathway. ..
  50. Groer M, El Badri N, Djeu J, Harrington M, Van Eepoel J. Suppression of natural killer cell cytotoxicity in postpartum women. Am J Reprod Immunol. 2010;63:209-13 pubmed publisher
    ..This suppressed NK cytotoxic effect may result as a response to interaction with tolerized fetal microchimeric cells accumulated during pregnancy in maternal blood and tissues. ..
  51. Warren E, Fujii N, Akatsuka Y, Chaney C, Mito J, Loeb K, et al. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Blood. 2010;115:3869-78 pubmed publisher
    ..This study has been registered at as NCT00107354. ..
  52. Dustin M, Long E. Cytotoxic immunological synapses. Immunol Rev. 2010;235:24-34 pubmed publisher
    ..This review provides an overview of work on cytotoxic immunological synapses and suggests pathways forward in applying this information to the development of therapeutic agents. ..
  53. Di Bonito P, Grasso F, Mangino G, Massa S, Illiano E, Franconi R, et al. Immunomodulatory activity of a plant extract containing human papillomavirus 16-E7 protein in human monocyte-derived dendritic cells. Int J Immunopathol Pharmacol. 2009;22:967-78 pubmed
    ..This is a propaedeutic study for a possible use of E7-containing plant extract in human immunotherapy of HPV-related lesions. ..