Key Points• CD20 Bdep therapy inhibits CD8 1 T-cell proliferation in vitro.• CD20 Bdep therapy prevents CD8 1 T-cell-mediated ITP in vivo.Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with a complex pathogenesis, which includes both antibody-and T-cell-mediated effector mechanisms. Rituximab (an anti-human CD20 monoclonal antibody [mAb]) is one of the treatments for ITP and is known to deplete B cells but may also work by affecting the T-cell compartments. Here, we investigated the outcome of B-cell depletion (Bdep) therapy on CD8 1 T-cell-mediated ITP using a murine model. CD61 knockout (KO) mice were immunized with CD611 platelets, and T-cell-mediated ITP was initiated by transfer of their splenocytes into severe combined immunodeficiency (SCID) mice. The CD61 KO mice were administrated an anti-mouse CD20 mAb either before or after CD61

Bleomycin has been suggested to incite plasma extravasation and influx of inflammatory cells leading to pulmonary fibrosis. We hypothesized that stable analogs of the 12-lipoxygenase product, hepoxilin, may attenuate these effects. We initially investigated the effects of the four hepoxilin analogs (PBT-1 to -4) coadministered intradermally with bleomycin and found that PBT-1 and -2 significantly opposed the vascular permeability effects of bleomycin in rat skin. We subsequently tested the hepoxilin analogs for their actions in opposing the intratracheal bleomycin-evoked acute inflammatory phase of lung fibrosis in the mouse, characterized by a marked accumulation of macrophages and an increase in the rate of collagen synthesis and deposition. We found that the bleomycin-evoked effects on macrophage influx were inhibited by all the hepoxilin analogs (PBT-1, -3, and -4 Ͼ PBT-2) administered i.p. for 8 days. Increased total lung collagen was completely abrogated by PBT-1 and -2, whereas PBT-3 and -4 had little effect. A doseresponse study with PBT-1 indicated that the effective dose for inhibition of bleomycin-induced inflammatory and histological changes was below 10 g/day. These studies demonstrate an in vivo action of stable analogs of hepoxilin and support an effect on inflammation and vascular permeability from these novel compounds, especially for PBT-1.Idiopathic pulmonary fibrosis is a devastating disorder that is poorly understood and resistant to treatment (Cooper, 2000). The observation that the antibiotic bleomycin sulfate (BL), a potent cancer chemotherapeutic agent (Adamson, 1984;Nici et al., 1998), may cause interstitial lung fibrosis in humans (Yagoda et al., 1972) led to the development of animal models in which a single dose of BL administered intratracheally induced changes resembling human idiopathic pulmonary fibrosis histopathologically (Kelley et al., 1980). The acute phase of this response is characterized by a marked accumulation of inflammatory cells and an increase in the rate of collagen synthesis and deposition (Cooper et al., 1988;Gurujeyalakshmi and Giri, 1995;Giri and Hollinger, 1996).Previous animal studies have demonstrated that BLevoked lung fibrosis is exacerbated with nordihydroguaiaretic acid, a lipoxygenase inhibitor, suggesting that a lipoxygenase product may be involved in endogenous mechanisms controlling lung fibrosis (Giri and Hollinger, 1996). The hepoxilins (HXs) may be candidates for the control of lung fibrosis as they are formed through the 12-lipoxygenase pathway of metabolism of arachidonic acid (Pace-Asciak et al., 1983;Pace-Asciak, 1984;Pace-Asciak and Martin, 1984). These compounds have previously been shown to have significant biological actions (Pace-Asciak, 1984;Dho et al., 1990;Laneuville et al., 1992;Pace-Asciak et al., 1995;Reynaud et al., 1996Reynaud et al., , 1999Sutherland et al., 2000). HXs raise free intracellular calcium in human neutrophils ex vivo through the release from stores and vascular tissue in vitro and block the intracellular calc...

IgG immune responsiveness against allogeneic PLT transfusions is dependent on recipient expression of I-E MHC class II molecules, whereas I-A expression is linked with CD8-mediated suppression of PLT immunity. The data suggest that strategies to modify recipient MHC class II presentation of donor PLT antigens would be effective in eliminating PLT alloimmunity.