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CellBio  2015 

The Cell Biology of Systemic Hyperinflammation Resulting from Failed Cytolytic Target Cell Killing

DOI: 10.4236/cellbio.2015.43005, PP. 37-45

Keywords: Cytokine Storms, Cytolytic T Lymphocytes (CTLs), Familial Hemophagocytic Lymphohistiocytosis (FHL), Natural Killer (NK) Cells, Hyperinflammation

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Abstract:

Mutations in genes encoding a key component of cytotoxic granules, or the machinery for their release, underlie the systemic hyperiflammatory symptoms of familial hemophagocytic lymphohistiocytosis (FHL), a typically pediatric onset autosomal recessive disorder with five known genetic subtypes (FHL1 - 5). FHL1 mutations have been mapped to chromosome 9, while the respective genes mutated in FHL2 (PRF1), FHL3 (UNC13D/Munc13-4), FHL4 (STX11) and FHL5 (STXBP2/ Munc18b/Munc18-2) have been identified. Perforin gene mutation directly affected the cytolytic activity of the cytotoxic granules. All the other FHL mutations appear to affect some aspect of cytotoxic granule exocytosis, resulting in impaired target cell killing by cytolytic T lymphocytes (CTLs) and/or natural killer (NK) cells. Recent findings suggest that failure to kill and detach from target cells, and prolonged synapse connection time, promote cytokine hypersecretion by the defective CTLs and NKs, which in turn result in systemic inflammation. Deciphering the genetics of FHL has contributed towards our understanding of the cell biology of hyperinflammatory responses and hemophagocytic lymphohistiocytosis accompanying pathological conditions such as cancer and viral infections.

 References

[1]  Trambas, C.M. and Griffiths, G.M. (2003) Delivering the Kiss of Death. Nature Immunology, 4, 399-403.
http://dx.doi.org/10.1038/ni0503-399
[2]  Pipkin, M.E. and Lieberman, J. (2007) Delivering the Kiss of Death: Progress on Understanding How Perforin Works. Current Opinion in Immunology, 19, 301-308.
http://dx.doi.org/10.1016/j.coi.2007.04.011
[3]  Voskoboinik, I., Dunstone, M.A., Baran, K., Whisstock, J.C. and Trapani, J.A. (2010) Perforin: Structure, Function, and Role in Human Immunopathology. Immunological Reviews, 235, 35-54.
http://dx.doi.org/10.1111/j.0105-2896.2010.00896.x
[4]  Thiery, J., Keefe, D., Boulant, S., Boucrot, E., Walch, M., Martinvalet, D., Goping, I.S., Bleackley, R.C., Kirchhausen, T. and Lieberman, J. (2011) Perforin Pores in the Endosomal Membrane Trigger the Release of Endocytosed Granzyme B into the Cytosol of Target Cells. Nature Immunology, 12, 770-777.
http://dx.doi.org/10.1038/ni.2050
[5]  Bots, M. and Medema, J.P. (2006) Granzymes at a Glance. Journal of Cell Science, 119, 5011-5014.
http://dx.doi.org/10.1242/jcs.03239
[6]  Voskoboinik, I., Whisstock, J.C. and Trapani, J.A. (2015) Perforin and Granzymes: Function, Dysfunction and Human Pathology. Nature Reviews Immunology, 15, 388-400.
http://dx.doi.org/10.1038/nri3839
[7]  Peters, P.J., Borst, J., Oorschot, V., Fukuda, M., Krähenbühl, O., Tschopp, J., Slot, J.W. and Geuze, H.J. (1991) Cytotoxic T Lymphocyte Granules Are Secretory Lysosomes, Containing Both Perforin and Granzymes. The Journal of Experimental Medicine, 173, 1099-1109.
http://dx.doi.org/10.1084/jem.173.5.1099
[8]  de Saint Basile, G., Ménasché, G. and Fischer, A. (2010) Molecular Mechanisms of Biogenesis and Exocytosis of Cytotoxic Granules. Nature Reviews Immunology, 10, 568-579.
http://dx.doi.org/10.1038/nri2803
[9]  Yokosuka, T. and Saito, T. (2010) The Immunological Synapse, TCR Microclusters, and T Cell Activation. Current Topics in Microbiology and Immunology, 340, 81-107.
http://dx.doi.org/10.1007/978-3-642-03858-7_5
[10]  Lopez, J.A., Susanto, O., Jenkins, M.R., Lukoyanova, N., Sutton, V.R., Law, R.H.P., Johnston, A., Bird, C.H., Bird, P.I., Whisstock, J.C., Trapani, J.A., Saibil, H.R. and Voskoboinik, I. (2013) Perforin Forms Transient Pores on the Target Cell Plasma Membrane to Facilitate Rapid Access of Granzymes during Killer Cell Attack. Blood, 121, 2659- 2668.
http://dx.doi.org/10.1182/blood-2012-07-446146
[11]  Susanto, O., Stewart, S.E., Voskoboinik, I., Brasacchio, D., Hagn, M., Ellis, S., Asquith, S., Sedelies, K.A., Bird, P.I., Waterhouse, N.J. and Trapani, J.A. (2013) Mouse Granzyme A Induces a Novel Death with Writhing Morphology That Is Mechanistically Distinct from Granzyme B-Induced Apoptosis. Cell Death & Differentiation, 20, 1183-1193.
http://dx.doi.org/10.1038/cdd.2013.59
[12]  Canna, S.W. and Behrens, E.M. (2012) Making Sense of the Cytokine Storm: A Conceptual Framework for Understanding, Diagnosing, and Treating Hemophagocytic Syndromes. Pediatric Clinics of North America, 59, 329-344.
http://dx.doi.org/10.1016/j.pcl.2012.03.002
[13]  Chandrakasan, S. and Filipovich, A.H. (2013) Hemophagocytic Lymphohistiocytosis: Advances in Pathophysiology, Diagnosis, and Treatment. Journal of Pediatrics, 163, 1253-1259.
http://dx.doi.org/10.1016/j.jpeds.2013.06.053
[14]  Mehta, R.S. and Smith, R.E. (2013) Hemophagocytic Lymphohistiocytosis (HLH): A Review of Literature. Medical Oncology, 30, 740.
http://dx.doi.org/10.1007/s12032-013-0740-3
[15]  Filipovich, A.H. and Chandrakasan, S. (2015) Pathogenesis of Hemophagocytic Lymphohistiocytosis. Hematology/ Oncology Clinics of North America, 29, 895-902.
http://dx.doi.org/10.1016/j.hoc.2015.06.007
[16]  Degar, B. (2015) Familial Hemophagocytic Lymphohistiocytosis. Hematology/Oncology Clinics of North America, 29, 903-913.
http://dx.doi.org/10.1016/j.hoc.2015.06.008
[17]  Tang, B.L. (2015) A Unique SNARE Machinery for Exocytosis of Cytotoxic Granules and Platelets Granules. Molecular Membrane Biology, 32, 120-126.
http://dx.doi.org/10.3109/09687688.2015.1079934
[18]  Parvaneh, N., Filipovich, A.H. and Borkhardt, A. (2013) Primary Immunodeficiencies Predisposed to Epstein-Barr Virus-Driven Haematological Diseases. British Journal of Haematology, 162, 573-586.
http://dx.doi.org/10.1111/bjh.12422
[19]  Yamazaki, S., Nakamura, F., Nasu, R., Nannya, Y., Ichikawa, M. and Kurokawa, M. (2011) Haemophagocytic Lymphohistiocytosis Is a Recurrent and Specific Complication of Acute Erythroid Leukaemia. British Journal of Haematology, 153, 669-672.
http://dx.doi.org/10.1111/j.1365-2141.2010.08544.x
[20]  Atteritano, M., David, A., Bagnato, G., Beninati, C., Frisina, A., Iaria, C. and Cascio, A. (2012) Haemophagocytic Syndrome in Rheumatic Patients. A Systematic Review. European Review for Medical and Pharmacological Sciences, 16, 1414-1424.
[21]  Cetica, V., Pende, D., Griffiths, G.M. and Aricò, M. (2010) Molecular Basis of Familial Hemophagocytic Lymphohistiocytosis. Haematologica, 95, 538-541.
http://dx.doi.org/10.3324/haematol.2009.019562
[22]  Sieni, E., Cetica, V., Mastrodicasa, E., Pende, D., Moretta, L., Griffiths, G. and Aricò, M. (2012) Familial Hemophagocytic Lymphohistiocytosis: A Model for Understanding the Human Machinery of Cellular Cytotoxicity. Cellular and Molecular Life Sciences, 69, 29-40.
http://dx.doi.org/10.1007/s00018-011-0835-y
[23]  Gholam, C., Grigoriadou, S., Gilmour, K.C. and Gaspar, H.B. (2011) Familial Haemophagocytic Lymphohistiocytosis: Advances in the Genetic Basis, Diagnosis and Management. Clinical & Experimental Immunology, 163, 271-283.
http://dx.doi.org/10.1111/j.1365-2249.2010.04302.x
[24]  Ohadi, M., Lalloz, M.R., Sham, P., Zhao, J., Dearlove, A.M., Shiach, C., Kinsey, S., Rhodes, M. and Layton, D.M. (1999) Localization of a Gene for Familial Hemophagocytic Lymphohistiocytosis at Chromosome 9q21.3-22 by Homozygosity Mapping. American Journal of Human Genetics, 64, 165-171.
http://dx.doi.org/10.1086/302187
[25]  Stepp, S.E., Dufourcq-Lagelouse, R., Le Deist, F., Bhawan, S., Certain, S., Mathew, P.A., Henter, J.I., Bennett, M., Fischer, A., de Saint Basile, G. and Kumar, V. (1999) Perforin Gene Defects in Familial Hemophagocytic Lymphohistiocytosis. Science, 286, 1957-1959.
http://dx.doi.org/10.1126/science.286.5446.1957
[26]  Trizzino, A., zur Stadt, U., Ueda, I., Risma, K., Janka, G., Ishii, E., Beutel, K., Sumegi, J., Cannella, S., Pende, D., Mian, A., Henter, J.I., Griffiths, G., Santoro, A., Filipovich, A. and Aricò, M., Histiocyte Society HLH Study Group (2008) Genotype-Phenotype Study of Familial Haemophagocytic Lymphohistiocytosis Due to Perforin Mutations. Journal of Medical Genetics, 45, 15-21.
http://dx.doi.org/10.1136/jmg.2007.052670
[27]  Rosado, C.J., et al. (2007) A Common Fold Mediates Vertebrate Defense and Bacterial Attack. Science, 317, 1548-1551.
http://dx.doi.org/10.1126/science.1144706
[28]  Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachée-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A. and de Saint Basile, G. (2003) Munc13-4 Is Essential for Cytolytic Granules Fusion and Is Mutated in a Form of Familial Hemophagocytic Lymphohistiocytosis (FHL3). Cell, 115, 461-473.
http://dx.doi.org/10.1016/S0092-8674(03)00855-9
[29]  Yamamoto, K., Ishii, E., Sako, M., Ohga, S., Furuno, K., Suzuki, N., Ueda, I., Imayoshi, M., Yamamoto, S., Morimoto, A., Takada, H., Hara, T., Imashuku, S., Sasazuki, T. and Yasukawa, M. (2004) Identification of Novel MUNC13-4 Mutations in Familial Haemophagocytic Lymphohistiocytosis and Functional Analysis of MUNC13-4-Deficient Cytotoxic T Lymphocytes. Journal of Medical Genetics, 41, 763-767.
http://dx.doi.org/10.1136/jmg.2004.021121
[30]  Meeths, M., et al. (2011) Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL3) Caused by Deep Intronic Mutation and Inversion in UNC13D. Blood, 118, 5783-5793.
http://dx.doi.org/10.1182/blood-2011-07-369090
[31]  Entesarian, M., Chiang, S.C.C., Schlums, H., Meeths, M., Chan, M.Y., Mya, S.N., Soh, S.Y., Nordenskjöld, M., Henter, J.I. and Bryceson, Y.T. (2013) Novel Deep Intronic and Missense UNC13D Mutations in Familial Haemophagocytic Lymphohistiocytosis Type 3. British Journal of Haematology, 162, 415-418.
http://dx.doi.org/10.1111/bjh.12371
[32]  Shirakawa, R., Higashi, T., Tabuchi, A., Yoshioka, A., Nishioka, H., Fukuda, M., Kita, T. and Horiuchi, H. (2004) Munc13-4 Is a GTP-Rab27-Binding Protein Regulating Dense Core Granule Secretion in Platelets. Journal of Biological Chemistry, 279, 10730-10737.
http://dx.doi.org/10.1074/jbc.M309426200
[33]  zur Stadt, U., Schmidt, S., Kasper, B., Beutel, K., Diler, A.S., Henter, J.I., Kabisch, H., Schneppenheim, R., Nürnberg, P., Janka, G. and Hennies, H.C. (2005) Linkage of Familial Hemophagocytic Lymphohistiocytosis (FHL) Type-4 to Chromosome 6q24 and Identification of Mutations in Syntaxin 11. Human Molecular Genetics, 14, 827-834.
http://dx.doi.org/10.1093/hmg/ddi076
[34]  Teng, F.Y., Wang, Y. and Tang, B.L. (2001) The Syntaxins. Genome Biology, 2, Reviews 3012.1-Reviews 3012.7.
[35]  Tang, B.L., Low, D.Y. and Hong, W. (1998) Syntaxin 11: A Member of the Syntaxin Family without a Carboxyl Terminal Transmembrane Domain. Biochemical and Biophysical Research Communications, 245, 627-632.
http://dx.doi.org/10.1006/bbrc.1998.8490
[36]  Prekeris, R., Klumperman, J. and Scheller, R.H. (2000) Syntaxin 11 Is an Atypical SNARE Abundant in the Immune System. European Journal of Cell Biology, 79, 771-780.
http://dx.doi.org/10.1078/0171-9335-00109
[37]  Zhang, S., Ma, D., Wang, X., Celkan, T., Nordenskjöld, M., Henter, J.I., Fadeel, B. and Zheng, C. (2008) Syntaxin-11 Is Expressed in Primary Human Monocytes/Macrophages and Acts as a Negative Regulator of Macrophage Engulfment of Apoptotic Cells and IgG-Opsonized Target Cells. British Journal of Haematology, 142, 469-479.
http://dx.doi.org/10.1111/j.1365-2141.2008.07191.x
[38]  Bryceson, Y.T., Rudd, E., Zheng, C., Edner, J., Ma, D., Wood, S.M., Bechensteen, A.G., Boelens, J.J., Celkan, T., Farah, R.A., Hultenby, K., Winiarski, J., Roche, P.A., Nordenskjöld, M., Henter, J.I., Long, E.O. and Ljunggren, H.G. (2007) Defective Cytotoxic Lymphocyte Degranulation in Syntaxin-11 Deficient Familial Hemophagocytic Lymphohistiocytosis 4 (FHL4) Patients. Blood, 110, 1906-1915.
http://dx.doi.org/10.1182/blood-2007-02-074468
[39]  Arneson, L.N., Brickshawana, A., Segovis, C.M., Schoon, R.A., Dick, C.J. and Leibson, P.J. (2007) Cutting Edge: Syntaxin 11 Regulates Lymphocyte-Mediated Secretion and Cytotoxicity. Journal of Immunology, 179, 3397-3401.
http://dx.doi.org/10.4049/jimmunol.179.6.3397
[40]  Müller, M.L., Chiang, S.C.C., Meeths, M., Tesi, B., Entesarian, M., Nilsson, D., Wood, S.M., Nordenskjöld, M., Henter, J.I., Naqvi, A. and Bryceson, Y.T. (2014) An N-Terminal Missense Mutation in STX11 Causative of FHL4 Abrogates Syntaxin-11 Binding to Munc18-2. Frontiers in Immunology, 4, 515.
http://dx.doi.org/10.3389/fimmu.2013.00515
[41]  zur Stadt, U., Rohr, J., Seifert, W., Koch, F., Grieve, S., Pagel, J., Strauss, J., Kasper, B., Nürnberg, G., Becker, C., Maul-Pavicic, A., Beutel, K., Janka, G., Griffiths, G., Ehl, S. and Hennies, H.C. (2009) Familial Hemophagocytic Lymphohistiocytosis Type 5 (FHL-5) Is Caused by Mutations in Munc18-2 and Impaired Binding to Syntaxin 11. American Journal of Human Genetics, 85, 482-492.
http://dx.doi.org/10.1016/j.ajhg.2009.09.005
[42]  Côte, M., Ménager, M.M., Burgess, A., Mahlaoui, N., Picard, C., Schaffner, C., Al-Manjomi, F., Al-Harbi, M., Alangari, A., Le Deist, F., Gennery, A.R., Prince, N., Cariou, A., Nitschke, P., Blank, U., El-Ghazali, G., Ménasché, G., Latour, S., Fischer, A. and de Saint Basile, G. (2009) Munc18-2 Deficiency Causes Familial Hemophagocytic Lymphohistiocytosis Type 5 and Impairs Cytotoxic Granule Exocytosis in Patient NK Cells. Journal of Clinical Investigation, 119, 3765-3773.
http://dx.doi.org/10.1172/JCI40732
[43]  Toonen, R.F.G. and Verhage, M. (2003) Vesicle Trafficking: Pleasure and Pain from SM Genes. Trends in Cell Biology, 13, 177-186.
http://dx.doi.org/10.1016/S0962-8924(03)00031-X
[44]  Bonifacino, J.S. and Glick, B.S. (2004) The Mechanisms of Vesicle Budding and Fusion. Cell, 116, 153-166.
http://dx.doi.org/10.1016/S0092-8674(03)01079-1
[45]  Halimani, M., Pattu, V., Marshall, M.R., Chang, H.F., Matti, U., Jung, M., Becherer, U., Krause, E., Hoth, M., Schwarz, E.C. and Rettig, J. (2014) Syntaxin11 Serves as a t-SNARE for the Fusion of Lytic Granules in Human Cytotoxic T Lymphocytes. European Journal of Immunology, 44, 573-584.
http://dx.doi.org/10.1002/eji.201344011
[46]  Ji, X., Chang, B., Naggert, J.K. and Nishina, P.M. (2016) Lysosomal Trafficking Regulator (LYST). Advances in Experimental Medicine and Biology, 854, 745-750.
http://dx.doi.org/10.1007/978-3-319-17121-0_99
[47]  Ménasché, G., Pastural, E., Feldmann, J., Certain, S., Ersoy, F., Dupuis, S., Wulffraat, N., Bianchi, D., Fischer, A., Le Deist, F. and de Saint Basile, G. (2000) Mutations in RAB27A Cause Griscelli Syndrome Associated with Haemophagocytic Syndrome. Nature Genetics, 25, 173-176.
http://dx.doi.org/10.1038/76024
[48]  Neeft, M., Wieffer, M., de Jong, A.S., Negroiu, G., Metz, C.H.G., van Loon, A., Griffith, J., Krijgsveld, J., Wulffraat, N., Koch, H., Heck, A.J.R., Brose, N., Kleijmeer, M. and van der Sluijs, P. (2005) Munc13-4 Is an Effector of rab27a and Controls Secretion of Lysosomes in Hematopoietic Cells. Molecular Biology of the Cell, 16, 731-741.
http://dx.doi.org/10.1091/mbc.E04-10-0923
[49]  Haddad, E.K., Wu, X., Hammer, J.A. and Henkart, P.A. (2001) Defective Granule Exocytosis in Rab27a-Deficient Lymphocytes from Ashen Mice. Journal of Cell Biology, 152, 835-842.
http://dx.doi.org/10.1083/jcb.152.4.835
[50]  Hume, A.N. and Seabra, M.C. (2011) Melanosomes on the Move: A Model to Understand Organelle Dynamics. Biochemical Society Transactions, 39, 1191-1196.
http://dx.doi.org/10.1042/BST0391191
[51]  Booth, A.E.G., Seabra, M.C. and Hume, A.N. (2012) Rab27a and Melanosomes: A Model to Investigate the Membrane Targeting of Rabs. Biochemical Society Transactions, 40, 1383-1388.
http://dx.doi.org/10.1042/BST20120200
[52]  Kimura, T., Kaneko, Y., Yamada, S., Ishihara, H., Senda, T., Iwamatsu, A. and Niki, I. (2008) The GDP-Dependent Rab27a Effector Coronin 3 Controls Endocytosis of Secretory Membrane in Insulin-Secreting Cell Lines. Journal of Cell Science, 121, 3092-3098.
http://dx.doi.org/10.1242/jcs.030544
[53]  Kurowska, M., Goudin, N., Nehme, N.T., Court, M., Garin, J., Fischer, A., de Saint Basile, G. and Ménasché, G. (2012) Terminal Transport of Lytic Granules to the Immune Synapse Is Mediated by the Kinesin-1/Slp3/Rab27a Complex. Blood, 119, 3879-3889.
http://dx.doi.org/10.1182/blood-2011-09-382556
[54]  Fukuda, M. (2002) The C2A Domain of Synaptotagmin-Like Protein 3 (Slp3) Is an Atypical Calcium-Dependent Phospholipid-Binding Machine: Comparison with the C2A Domain of Synaptotagmin I. Biochemical Journal, 366, 681-687.
http://dx.doi.org/10.1042/bj20020484
[55]  Matti, U., Pattu, V., Halimani, M., Schirra, C., Krause, E., Liu, Y., Weins, L., Chang, H.F., Guzman, R., Olausson, J., Freichel, M., Schmitz, F., Pasche, M., Becherer, U., Bruns, D. and Rettig, J. (2013) Synaptobrevin2 Is the v-SNARE Required for Cytotoxic T-Lymphocyte Lytic Granule Fusion. Nature Communications, 4, 1439.
http://dx.doi.org/10.1038/ncomms2467
[56]  Loo, L.S., Hwang, L.A., Ong, Y.M., Tay, H.S., Wang, C.C. and Hong, W. (2009) A Role for Endobrevin/VAMP8 in CTL Lytic Granule Exocytosis. European Journal of Immunology, 39, 3520-3528.
http://dx.doi.org/10.1002/eji.200939378
[57]  Valdez, A.C., Cabaniols, J.P., Brown, M.J. and Roche, P.A. (1999) Syntaxin 11 Is Associated with SNAP-23 on Late Endosomes and the Trans-Golgi Network. Journal of Cell Science, 112, 845-854.
[58]  Mollinedo, F., Calafat, J., Janssen, H., Martín-Martín, B., Canchado, J., Nabokina, S.M. and Gajate, C. (2006) Combinatorial SNARE Complexes Modulate the Secretion of Cytoplasmic Granules in Human Neutrophils. Journal of Immunology, 177, 2831-2841.
http://dx.doi.org/10.4049/jimmunol.177.5.2831
[59]  Martín-Martín, B., Nabokina, S.M., Blasi, J., Lazo, P.A. and Mollinedo, F. (2000) Involvement of SNAP-23 and Syntaxin 6 in Human Neutrophil Exocytosis. Blood, 96, 2574-2583.
[60]  Naegelen, I., Plançon, S., Nicot, N., Kaoma, T., Muller, A., Vallar, L., Tschirhart, E.J. and Bréchard, S. (2015) An Essential Role of Syntaxin 3 Protein for Granule Exocytosis and Secretion of IL-1α, IL-1β, IL-12b, and CCL4 from Differentiated HL-60 Cells. Journal of Leukocyte Biology, 97, 557-571.
http://dx.doi.org/10.1189/jlb.3A0514-254RR
[61]  Hackmann, Y., Graham, S.C., Ehl, S., Höning, S., Lehmberg, K., Aricò, M., Owen, D.J. and Griffiths, G.M. (2013) Syntaxin Binding Mechanism and Disease-Causing Mutations in Munc18-2. Proceedings of the National Academy of Sciences of the United States of America, 110, E4482-E4491.
http://dx.doi.org/10.1073/pnas.1313474110
[62]  Marshall, M.R., Pattu, V., Halimani, M., Maier-Peuschel, M., Müller, M.L., Becherer, U., Hong, W., Hoth, M., Tschernig, T., Bryceson, Y.T. and Rettig, J. (2015) VAMP8-Dependent Fusion of Recycling Endosomes with the Plasma Membrane Facilitates T Lymphocyte Cytotoxicity. Journal of Cell Biology, In Press.
[63]  Jenkins, M.R., Rudd-Schmidt, J.A., Lopez, J.A., Ramsbottom, K.M., Mannering, S.I., Andrews, D.M., Voskoboinik, I. and Trapani, J.A. (2015) Failed CTL/NK Cell Killing and Cytokine Hypersecretion Are Directly Linked through Prolonged Synapse Time. Journal of Experimental Medicine, 212, 307-317.
http://dx.doi.org/10.1084/jem.20140964
[64]  Trapani, J.A., Voskoboinik, I. and Jenkins, M.R. (2015) Perforin-Dependent Cytotoxicity: “Kiss of Death” or Prolonged Embrace with Darker Elocation-Idnseque11es? Oncoimmunology, 4, Article ID: e1036215.
http://dx.doi.org/10.1080/2162402X.2015.1036215
[65]  Jessen, B., Kögl, T., Sepulveda, F.E., de Saint Basile, G., Aichele, P. and Ehl, S. (2013) Graded Defects in Cytotoxicity Determine Severity of Hemophagocytic Lymphohistiocytosis in Humans and Mice. Frontiers in Immunology, 4, 448.
http://dx.doi.org/10.3389/fimmu.2013.00448
[66]  Sepulveda, F.E., Debeurme, F., Ménasché, G., Kurowska, M., Côte, M., Pachlopnik Schmid, J., Fischer, A. and de Saint Basile, G. (2013) Distinct Severity of HLH in Both Human and Murine Mutants with Complete Loss of Cytotoxic Effector PRF1, RAB27A, and STX11. Blood, 121, 595-603.
http://dx.doi.org/10.1182/blood-2012-07-440339
[67]  Kögl, T., Müller, J., Jessen, B., Schmitt-Graeff, A., Janka, G., Ehl, S., zur Stadt, U. and Aichele, P. (2013) Hemophagocytic Lymphohistiocytosis in Syntaxin-11-Deficient Mice: T-Cell Exhaustion Limits Fatal Disease. Blood, 121, 604- 613.
http://dx.doi.org/10.1182/blood-2012-07-441139
[68]  Zhang, K., Jordan, M.B., Marsh, R.A., Johnson, J.A., Kissell, D., Meller, J., Villanueva, J., Risma, K.A., Wei, Q., Klein, P.S. and Filipovich, A.H. (2011) Hypomorphic Mutations in PRF1, MUNC13-4, and STXBP2 Are Associated with Adult-Onset Familial HLH. Blood, 118, 5794-5798.
http://dx.doi.org/10.1182/blood-2011-07-370148
[69]  Meeths, M., Chiang, S.C.C., Löfstedt, A., Müller, M.L., Tesi, B., Henter, J.I. and Bryceson, Y.T. (2014) Pathophysiology and Spectrum of Diseases Caused by Defects in Lymphocyte Cytotoxicity. Experimental Cell Research, 325, 10-17.
http://dx.doi.org/10.1016/j.yexcr.2014.03.014
[70]  Clementi, R., Locatelli, F., Dupré, L., Garaventa, A., Emmi, L., Bregni, M., Cefalo, G., Moretta, A., Danesino, C., Comis, M., Pession, A., Ramenghi, U., Maccario, R., Aricò, M. and Roncarolo, M.G. (2005) A Proportion of Patients with Lymphoma May Harbor Mutations of the Perforin Gene. Blood, 105, 4424-4428.
http://dx.doi.org/10.1182/blood-2004-04-1477
[71]  Machaczka, M., Klimkowska, M., Chiang, S.C.C., Meeths, M., Müller, M.L., Gustafsson, B., Henter, J.I. and Bryceson, Y.T. (2013) Development of Classical Hodgkin’s Lymphoma in an Adult with Biallelic STXBP2 Mutations. Haematologica, 98, 760-764.
http://dx.doi.org/10.3324/haematol.2012.073098
[72]  Ravelli, A., Grom, A.A., Behrens, E.M. and Cron, R.Q. (2012) Macrophage Activation Syndrome as Part of Systemic Juvenile Idiopathic Arthritis: Diagnosis, Genetics, Pathophysiology and Treatment. Genes & Immunity, 13, 289-298.
http://dx.doi.org/10.1038/gene.2012.3
[73]  Deiva, K., Mahlaoui, N., Beaudonnet, F., de Saint Basile, G., Caridade, G., Moshous, D., Mikaeloff, Y., Blanche, S., Fischer, A. and Tardieu, M. (2012) CNS Involvement at the Onset of Primary Hemophagocytic Lymphohistiocytosis. Neurology, 78, 1150-1156.
http://dx.doi.org/10.1212/WNL.0b013e31824f800a

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