In this model, AR derived from human T cells would be expressed mainly in response to tissue injury, consistent with the importance of the local environmental signals for AR regulation. This contrasts with the requirement for specific effector mechanisms to combat different pathogens, in which pre-commitment to cytokine effector phenotypes (thus linking antigen and effector specificities) may be more effective for regulating clearance functions. Collectively, the coordinate inhibition of pro-inflammatory cytokines and induction of tissue-remodeling cytokines of the EGF family may represent a switch from pathogen clearance to tissue repair mechanisms by effector human T cells. Figure S1 Mouse Th2 but not Th1 cells express AR in response to TCR activation. In vitro induced allogeneic Th1 and Th2 cell lines [50] from B6PL or AR 2/2 mice were stimulated with plate-coated anti-CD3 (2 mg/mL) + anti-CD28 (1 mg/mL) antibodies for 6 hours. Expression of AR, IFNc and IL-4 in CD4 T cells was analyzed by ICS. Biotinylated goat antimouse AR antibodies were obtained from R&D Systems. LEAF TM purified anti-mouse CD3e (145-2C11) and LEAF TM purified antimouse CD28 (37.51) were purchased from BioLegend. APC-Cy7 conjugated anti-mouse CD3 (17A2), Alexa Fluor 700 conjugated anti-mouse CD4 (GK1.5), Pacific Blue conjugated anti-mouse CD44 (IM7), PerCP-Cy5.5 conjugated anti-mouse CD69 (H1.2F3), APC conjugated anti-mouse IL-2 (JES6-5H4), PE-Cy7 conjugated anti-mouse IL-4 (BVD6-24G2), PE conjugated antimouse IL-5 (TRFK5), and FITC-conjugated streptavidin were obtained from eBioscience. PE-Alexa Fluor 610 conjugated antimouse IFNc (XMG1.2) was obtained from Invitrogen. Similar results were obtained in at least three experiments. (TIF) Allo-SCT for multiple myeloma: a review of outcomes at a single transplant center Allogeneic stem cell transplant for multiple myeloma (MM) is one treatment associated with long-term disease-free survival. The high incidence of treatment-related mortality and relapses, however, are important reasons for controversy about the role of allografting in the management of MM. We reviewed our results of allografting for MM spanning a period of 34 years in order to better define long-term outcomes and identify areas of progress as well as areas requiring improvement. A total of 278 patients received allogeneic marrow or PBSCs after high-dose myeloablative (N=144) or reduced intensity, non-myeloablative (N=134) regimens. In multivariable analysis, adjusting for differences in patient groups, reduced intensity/non-myeloablative transplants were associated with significantly less acute GVHD, lower transplant mortality, better PFS and overall survival. There were no significant differences in relapse, progression or chronic GVHD, when adjusted. In multivariable analysis of patients receiving only non-myeloablative transplants, decreased overall survival and PFS were associated with relapse after a prior autograft and a β2 microglobulin >4.0. Transplant mortality was reduced and only influenced by a prior tandem autograft. The survival of patients with multiple myeloma (MM) has improved over the last decade as a result of melphalan-based high-dose therapy followed by auto-SCT, the introduction of novel anti-myeloma agents with increased efficacy in relapsed and refractory MM, and improvements in supportive care. 1 --6 Registry data indicate an improvement in median survival from 3 to 5 years, primarily among younger patients, as a result of these treatment innovations. 7 Despite these new developments, MM remains an incurable disease for the large majority, as all but a few patients will relapse. Allogeneic hematopoietic cell transplantation is currently one treatment with a potential for long-term disease control although its curative potential is debated. This is in part due to the graft-vs-myeloma effect, mediated by immune competent donor lymphocytes, best illustrated by the induction of sustained (molecular) remissions following donor lymphocyte infusions, 8 but could also be due in part to absence of contaminating myeloma cells in the donor graft and documented lower levels of residual disease. 9, 10 The role of allo-SCT in MM, however, is controversial due to the high mortality and morbidity associated with conventional myeloablative regimens and because convincing evidence for a survival benefit is lacking. 11 --13 In the last decade, non-myeloablative allo-SCT has gained in popularity due to significantly reduced TRM. 14, 15 Among four reports comparing auto-SCT with allo-SCT, two have shown survival advantages for the nonmyeloablative approach when compared with tandem autologous transplantation. 16 --19 A recently reported US clinical trial prospectively comparing tandem autologous transplant to autologous followed by non-myeloablative allo-SCTs found no differences in PFS or OS at 3 years. 20 In contrast, a European multicenter trial found than tandem autologous, non-myeloablative allo-SCT resulted in superior OS compared with single or tandem auto-SCT. 19 Furthermore, at least one registry report comparing conventional ablative with non-myeloabalative/reduced intensity allo-SCTs have shown similar survival outcomes with lower TRM for patients receiving non-ablative transplants yet higher rates of relapse and PFS inferior to ablative allo-SCT. 21 We reviewed our results of allo-SCT for patients with MM beginning in 1975 with the aim of identifying factors associated with improvements in disease-free survival and OS as preparative regimens have changed from ablative to non-myeloablative.