Autoimmune Lymphoproliferative Syndrome: Types I, II and Beyond
An essential element in the maintenance of homeostasis of the immune system is the capacity for apoptosis, or programmed cell death. Apoptosis limits the accumulation of lymphocytes, and minimizes reactions against self-antigen that can lead to autoimmunity1,2. Lymphocyte apoptosis occurs in at least two major forms: antigen receptor engagement and lymphokine withdrawal. These forms of death are controlled in a negative feedback mechanism termed propriocidal regulation1,3. Antigen-mediated death of lymphocytes is regulated by Fas (CD95/APO-1), tumor necrosis factor receptor (TNFR), and related molecules4-6. Passive apoptosis via lymphokine withdrawal may result from the cytoplasmic activation of caspases that is closely regulated by the mitochondria and the members of the Bcl-2 family of proteins. Apoptosis of other immune cells such as dendritic cells may also contribute to immune homeostasis7.
KeywordsLymphoma Anemia Polypeptide Leucine Phenylalanine
Unable to display preview. Download preview PDF.
- 12.Sneller MC, Wang J, Dale JK, Strober W, Middleton LA, Choi Y, Fleisher TA, Lim MS, Jaffe ES, Puck JM, Lenardo MJ, Straus SE: Clincial, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis. Blood 89: 1341–1348, 1997PubMedGoogle Scholar
- 13.Fuss IJ, Strober W, Dale JK, Fritz S, Pearlstein GR, Puck JM, Lenardo MJ, Straus SE: Characteristic T helper 2 T cell cytokine abnormalities in autoimmune lymphoproliferative syndrome, a syndrome marked by defective apoptosis and humoral autoimmunity. J Immunol 158: 1912–1918, 1997PubMedGoogle Scholar
- 22.Infante AJ, Britton HA, DeNapoli T, Middleton LA, Lenardo MJ, Jackson CE, Wang J, Fleisher T, Straus SE. Puck JM: The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis. J Pediatr 133: 629–633, 1998PubMedCrossRefGoogle Scholar
- 24.Chan F, Chun HJ, Zheng L, Bui K, Siegel RM, Lenardo MJ: A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science, in pressGoogle Scholar
- 25.Siegel R, Frederiksen JK, Zacharias DA, Chan FK, Johnson M, Lynch D, Tsien RY, Lenardo MJ: Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations. Science, in pressGoogle Scholar
- 26.Dianzani U, Bragardo M, DiFranco D, Alliaudi C, Scagni P, Buonfiglio D, Redoglia V, Bonissoni S, Correra A, Dianzani I, Ramenghi U: Deficiency of the Fas apoptosis pathway without Fas gene mutations in pediatric patients with autoimmunity/lymphoproliferation. Blood 89: 2871–2879, 1997PubMedGoogle Scholar
- 31.Muzio M. Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM: FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex. Cell 85: 817–827, 1996PubMedCrossRefGoogle Scholar
- 33.Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P, Wallach D: Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apol, and DR3 and is lethal prenatally. Immunity 9: 267–276, 1998PubMedCrossRefGoogle Scholar