Biology and Genetics of Hybrid Resistance

Bennett, Michael V. L.

doi:10.1016/s0065-2776(08)60034-6

Cited by 166 publications

(95 citation statements)

References 506 publications

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“…Briefly, target cells were incubated with 3.7 MBq/ml of Na 2 51 CrO 4 (Amersham Corp.) in RPMI 1640 with 25 mM Hepes and 10% FCS for 1 h at 37°C in an atmosphere of 5% CO 2 /humidified air, washed three times, and added to effector cells in U-bottomed 96-well plates. The effector:target ratio (E:T) was always 50:1 unless otherwise stated.…”

Section: Chemicalsmentioning

confidence: 99%

“…Natural killer (NK) 1 cells constitute a distinct lineage of lymphocytes (1) with the innate ability to specifically recognize and kill certain normal allogeneic leukocytes (2,3), tumor cells, and virally infected cells (4,5) by direct cell-mediated cytotoxicity. The presence of both activating and inhibitory NK cell receptors have been implicated in regulation of NK cytolysis.…”

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confidence: 99%

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Selective Activation of cAMP-dependent Protein Kinase Type I Inhibits Rat Natural Killer Cell Cytotoxicity

Torgersen

Vaage²,

Levy

et al. 1997

Journal of Biological Chemistry

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The present study examines the expression and involvement of cAMP-dependent protein kinase (PKA) isozymes in cAMP-induced inhibition of natural killer (NK) cell-mediated cytotoxicity. Rat interleukin-2-activated NK cells express the PKA ␣-isoforms RI␣, RII␣, and C␣ and contain both PKA type I and type II. Prostaglandin E 2 , forskolin, and cAMP analogs all inhibit NK cell lysis of major histocompatibility complex class I mismatched allogeneic lymphocytes as well as of standard tumor target cells. Specific involvement of PKA in the cAMP-induced inhibition of NK cell cytotoxicity is demonstrated by the ability of a cAMP antagonist, (R p )-8-Br-adenosine 3 ,5 -cyclic monophosphorothioate, to reverse the inhibitory effect of complementary cAMP agonist (S p )-8-Br-adenosine 3 ,5 -cyclic monophosphorothioate. Furthermore, the use of cAMP analog pairs selective for either PKA isozyme (PKA type I or PKA type II), shows a preferential involvement of the PKA type I isozyme, indicating that PKA type I is necessary and sufficient to completely abolish killer activatory signaling leading to NK cell cytotoxicity. Finally, combined treatment with phorbol ester and ionomycin maintains NK cell cytotoxicity and eliminates the cAMP-mediated inhibition, demonstrating that protein kinase C and Ca 2؉ -dependent events stimulate the cytolytic activity of NK cells at a site distal to the site of cAMP/PKA action.Natural killer (NK) 1 cells constitute a distinct lineage of lymphocytes (1) with the innate ability to specifically recognize and kill certain normal allogeneic leukocytes (2, 3), tumor cells, and virally infected cells (4, 5) by direct cell-mediated cytotoxicity. The presence of both activating and inhibitory NK cell receptors have been implicated in regulation of NK cytolysis. As formulated in the "missing self" hypothesis (6), a no-kill signal is induced by specific interaction of "self" MHC class I molecules with inhibitory NK receptors. Therefore, the presence of intracellular signaling pathways down-regulating or inhibiting the cytotoxic response may be important in preventing killing of normal autologous cells. In contrast to the "self" MHC class I-induced inhibition of natural killing, activating receptors have not been characterized to the same extent. However, both foreign MHC antigens on normal allogeneic cells and non-MHC antigens expressed on tumor cells have been demonstrated to interact with yet not fully characterized activating NK cell receptors (7-10). The present view is that NK cytotoxicity is a result of a fine balance between negative and positive signals induced through distinct sets of receptors inhibiting or activating the cytolytic activity (11).The second messenger cAMP regulates a number of cellular processes (12, 13). With the exception of certain ion channels, directly regulated by cAMP (14, 15), all known effects of cAMP are mediated via activation of cAMP-dependent protein kinase (PKA). The inactive PKA holoenzyme is a tetramer consisting of two regulatory (R) and two catalytic (C) subunits (16)....

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Section: Chemicalsmentioning

confidence: 99%

mentioning

confidence: 99%

Selective Activation of cAMP-dependent Protein Kinase Type I Inhibits Rat Natural Killer Cell Cytotoxicity

Torgersen

Vaage²,

Levy

et al. 1997

Journal of Biological Chemistry

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“…The BM was flushed out from the right tibia. The spleen and BM cells were then filtered through a 70-mm nylon cell strainer and centrifuged for 10 min at 350 Â g. Red blood cells were lysed with 0.8% NH 4 Cl before incubation of the samples for 20 min at 37 8C. FH with 5% BSA was added to the cell suspensions, followed by centrifugation (350 Â g, 10 min) and respuspension in a standard washing solution consisting of PBS with 2% FCS and 10 mmol/l NaN 3 .…”

Section: Ratsmentioning

confidence: 99%

“…T cells of the graft may recognize MHC antigens of the host and initiate a graft versus host reaction that may be lethal, but which is sometimes necessary for proper donor cell engraftment and proliferation [1±3]. Conversely, host immunocompetent cells that have survived an immunoablative pretreatment, may attack and eliminate the graft, in a host versus graft reaction [4,5]. The mechanisms behind the latter are not completely understood, but T as well as NK cells may participate.…”

Section: Introductionmentioning

confidence: 99%

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Long‐Term Donor Chimerism after MHC (RT1) Mismatched Bone Marrow Transplantation in the Rat: the Role of Host Alloreactive NK Cells

Engh¹,

Strøm-Gundersen

Benestad

et al. 2001

Scand J Immunol

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We have investigated the role of major histocompatibility complex (MHC) (RT1) disparities in the engraftment of bone marrow (BM) cells after whole body irradiation of rats. Mononuclear BM cells from PVG.RT7.2 (RT1 c ) rats were injected i.v. into sublethally (10Gy) whole body irradiated PVG (RT1 c ) rats and RT1 congenic and recombinant PVG rats. Repopulation of the BM, spleen, and blood with donor cells was assessed by FACS analysis of cells labelled with the fluorescein isothiocyanate (FITC)-labelled HIS41 monoclonal antibody (MoAb) against the RT7.2 marker. In RT1 matched (PVG.RT7.2 3 PVG) and RT1-mismatched combinations (PVG.RT7.2 3 PVG.1AV1), where radioresistant host natural killer (NK) cells could not recognize the BM inoculum as foreign, a donor chimerism close to 100% was observed after 6±8 weeks. However, in rat strain combinations where host NK cells could recognize an RT1 mismatch, almost no donor cells survived, and the rats were repopulated with leukocytes of host origin. In intra-MHC recombinant rat strains the element determining rejection or acceptance of the allograft mapped to the RT1-B/D-C/E/M region in PVG.R8 and PVG.R23 rats, in accordance with the patterns of NK alloreactivity in these strain combinations. NK cells may therefore be a primary obstacle to successful allogeneic BM engraftment in this model.

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