Activation-induced cell death

TCDD) induces Fas-dependent activation-induced cell death in superantigen primed T cells, Arch. Toxicol., 76, 570, 2002. 

Shi, Y.F., Sahai, B.M., and Green, D.R. Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes. Nature, 339, 625, 1989... 

Programmed cell death plays an important role during lymphocyte development, by eliminating autoreactive cells, as well as in the effector phase of the immune response, when antigen induced cell death halt cell activation. Several groups have been studied the function of PTEN in the immune response. PTEN heterozygous (PTEN+/-) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired in Pten+/-mice, and T lymphocytes from these mice show reduced activation-induced cell death and increased proliferation upon activation. PI3-K inhibitors restored Fas responsiveness in PTEN+/- cells. These results indicate that PTEN is an essential mediator of the Fas response and a repressor of autoimmunity, thus implicate the P13-Kinase/Akt pathway in Fas-mediated apoptosis (DiCristofano et al, 1999)... 

Accornero P, Radrizzani M, Care A, Mattia G, Chiodoni C, Kurrle R, Colombo MP (1998) HIV/gpl2 and PMA/ionomydn induced apoptosis but not activation induced cell death require PKC for Fas-L upregulation. FEBS Lett 436 467-465... 

Figure 22.2 Cellular activation by CpG DNA. CpG DNA directly activates dendritic cells (DCs), monocytes and macrophages, to express increased levels of co-stimu-latory molecules, to increase antigen presentation, and to secrete high levels of chemokines and cytokines, such as interleukin 12 (IL-12), interferon-a(IFN-a), and tumor necrosis factor-a (TNF-a), and monocytes and macro-phages have increased antibody-dependent cellular cytotoxicity (ADCC) activity. NK cells are induced to express IFN-7 by these cytokines acting in concert with CpG, and have increased lytic activity. B cells rapidly produce IL-b and IL-10 and express increased levels of costimulatory molecules. B cells rapidly enter the cell cycle and become resistant to some forms of activation-induced cell death. T cells are not directly activated by CpG, but because of the T helper 1 (Thl)-like cytokine environment, and the increased antigen presenting cell (APC) activity, antigen-specific Thl cells and cytotoxic T lymphocytes (CTL) are generated.

Goda C, Kanaji T, Kanaji S,Tanaka G, Arima K, Ohno S, Izuhara K. Involvement of IL-32 in activation-induced cell death in T cells. Inti Immunol 2006 18 233 40. 

Lee H, Cha S, Lee M-S, Cho G-J, Choi WS, Suk K (2003) Role of antiproliferative B cell transla-cation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microgUa. J... 

Switzer, K.C., Fan, Y.Y., Wang, N., McMurray, D.N., and Chapkin, R.S. 2004. Dietary n-3 polyunsaturated fatty acids promote activation-induced cell death in Thl-polarized murine CD4+ T cells. J. Lipid Res. 45, 1482-1492. 

Further effector functions of Tcells are targeted by l,25(OH)2D3 CD178 (FasL) is downregulated on l,25(OFI)2D3 treated T cells thereby conferring protection from activation-induced cell death [105],... 

Alderson MR, Tough TW, Davis-Smith T, Braddy S, Falk B, Schooley KA, Goodwin RG, Smith CA, Ramsdell F, Lynch DH Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med 1995 181 71-77. 

While the observations summarized above might imply that Th2 cells are more resistant to SEB-induced apoptosis than Thl cells in subjects with normal cytokine balances, studies of polarized T cell lines indicate that Th2 cells are more resistant to activation-induced cell death than Thl cells [50, 51]. Consistently, T cell responses to SAgs usually involve Thl cells and release of the cytokines IL-2, TNF-(3, and INF-y, rather than the usual pattern of induction of a Th2 response by exotoxins, which leads to the production of antibody to the exotoxin. It remains to be seen whether B cell SAgs target preferentially Bel or Be2 cells [52],... 

Varadhachary AS, Perdow SN, Hu C, Ramanarayanan M, Salgame P Differential ability of T cell subsets to undergo activation-induced cell death. Proc Natl Acad Sci USA 1997 94 5778-5783. 

Aikoh T, Tomokuni A, Matsukii T, Hyodoh F, Ueki H, Otsuki T, Ueki A (1998) Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro. Int J Oncol, 12 1355-1359. 

Green DR, Drain N, Pinkoski M (2003) Activation-induced cell death in T cells. Immunol Rev, 193 70-81. 

McKallip RJ, Do Y, Eisher MT, Robertson JL, Nagarkatti PS, Nagarkatti M. Role of CD44 in activation-induced cell death CD44-deficient mice exhibit enhanced T cell response to conventional and superantigens. Int Immunol 2002 14 1015-1026. 

Brunner, T., Yoo, N. J., LaFace, D., Ware, C. F., and Green, D. R. (1996). Activation-induced cell death in murine T cell hybridomas. Differential regulation of Fas (CD95) versus Fas ligand expression by cyclosporin A and FK506. Int. Immunol. 8, 1017-1026. 

In mature T cells, activation of the TCR induces proliferation via an autocrine mechanism by stimulating the synthesis of both IL-2 and IL-2 receptor (Meuer et al., 1984). On withdrawal of IL-2 these cell undergo apoptosis by a mechanism that requires synthesis of both protein and RNA (Duke and Cohen, 1986). However, if IL-2 or other growth factors are available, these cells proliferate for 3-4 days, after which time they undergo apoptosis, a phenomenon referred to as activation-induced cell death (AICD). Protein and RNA synthesis is required at the time of activation for AICD to proceed (Shi et al., 1989 Ucker et al., 1989 Green and Scott, 1994). Although not strictly developmental cell death, AICD has been used to study the involvement of molecules such as Fas (see Section 3.2) and Myc (see Section 5.2) in the T cell. 

Jin, L.W., Inaba, K. and Saitoh, T. (1992) The involvement of protein kinase C in activation-induced cell death in T-cell hybridoma. Cell Immunol. 144 217-227. 

Maher, S., Toomey, D., Condron, C. and Bouchier-Hayes, D. (2002) Activation induced cell death the controversial role of Fas and Fas ligand in immune privilege and tumour counterattack. Immunol.Cell Biol. 80 131-137. 

Janssen EM, Droin NM, Lemmens EE et al. CD4 T-cell help controls CD8 T-cell memory via TRAIL-mediated activation-induced cell death. Nature 2005 434 88-93. 

Intratracheal instillation of sihca (20 mg in 50 (ji sterile saline) into BALB/c mice reduced mitogenic responses to T cell receptor stimulation, and markedly increased activation-induced cell death, compared with control lymphocytes from sahne-instilled mice (Borges et al. 2002). CD4 T cell death was mediated by Fas ligand, because CD4 T cells from Fas ligand-deficient gld mice did not suffer activation-induced apoptosis. 

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