Faculty Opinions recommendation of Prevention of graft-versus-host disease by intra-bone marrow injection of donor T cells.

2007 ◽  
Author(s):  
Ignazio Majolino
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells

The Role of Selective Depletion of Alloreactive Donor T Cells in Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5167-5167
Author(s):  
Yihuan Chai ◽  
Huiying Qiu ◽  
Hui Lv
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Allogeneic Bone Marrow ◽  
Third Party ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells

Abstract One of the main goals in allogeneic bone marrow(BM) transplantation is the abrogation of graft-versus-host disease (GVHD) with the preservation of antileukemia and antiviral activity. The Study present a selective T cell depletion strategy based on the physical separation of the alloreactive T cells, which were identified by expression of two activation-induced antigens (CD25 and CD69). T cells from C57BL/6(H-2b) mice were first activated with BALB/c (H-2d) recipient spleen cells in a 2-day mixed-lymphocyte-culture (MLC). Following this activation, this compound is selectively depleted based on expression of two activation-induced antigens CD25 and CD69 using magnetic cell sorting. The depleted cells or the untreated cells were then rechallenged respectively in a secondary MLC, with the same stimulator cells or a third-party (DBAH-2k) or tumor- specific (SP2/0, BALB/c-origin myeloma) cells. Cells proliferation were assayed at the indicated time points(1, 2, 3, 4, 5 days). These treated cells or control-cultured cells (2.0×106) mixed with 5.0×106 BM cells from C57BL/6 were transfused respectively by the trail vain into the lethally irradiated BALB/c to observe the survival time, GVHD incidence and pathological analysis. MLC assays demonstrated that this technique led to a significant decrease in alloreactivity of donor cells(29.02~64.17%), which at the same time preserved reactivity against third party cells(49.61~75.69%)and anti-tumor cells(61.14~68.62%). The mice in the group of control-coclutured were died of acute GVHD within 24days. The 7 recipient mice in the treated group were free of acute GVHD, and 3 mice were died of acute GVHD (aGVHD) within 23 days. MACS-based ex-vivo depletion of alloreactive donor T cells based on expression of two activation-induced antigens (CD25 and CD69) could inhibit anti-host responses, by contrast, anti-SP2/O and anti-third-party responses were preserved. Cotransplantation of these selected depleted cells and BM cells could reduce aGVHD.

scholarly journals Patient Bone Marrow Chimerism at Time of Donor Lymphocyte Infusion Predicts Development of Graft Versus Host Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2132-2132
Author(s):  
Eva AS Koster ◽  
Liesbeth C. de Wreede ◽  
Sylwia Wallet-Malicka ◽  
Lisette Bogers ◽  
Peter van Balen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Hazard Ratio ◽  
The State ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells ◽  
Donor Type

Abstract After allogeneic stem cell transplantation (alloSCT), donor T cells targeting patient derived hematopoietic cells can induce a Graft versus Leukemia (GvL) effect preventing relapse. However, targeting of healthy patient tissues can cause Graft versus Host Disease (GvHD). The inflammatory environment induced by pre transplantation conditioning, the number of donor T cells in the graft, genetic disparity between patient and donor and the presentation of allo-antigens by activated patient derived antigen-presenting cells (APC) to donor T cells play a role in the development of GvL and/or GvHD. Donor T cell depletion (TCD) reduces GvHD and GvL. After TCD alloSCT, postponed prophylactic donor lymphocyte infusions (pDLI) are often needed to induce a GvL effect. When using 10/10 matched donors, our first dose of pDLI at six months after TCD alloSCT contained 3.0x10^6 T cells/kg (related donor, RD) or 1.5x10^6 T cells/kg (unrelated donor, UD). We evaluated whether the risk of developing GvHD after DLI is influenced by the donor type, intensity of the conditioning and/or patient bone marrow (BM) chimerism at time of DLI Sixty patients with acute leukemia (52 AML, 8 ALL; median age 57; 27 RD, 33 UD) received pDLI at a median of 6.4 months after TCD alloSCT in the absence of GVHD or relapse. Twenty-four patients received myeloablative (MA) conditioning consisting of cyclophosphamide and TBI. 36 patients received non-myeloablative (NMA) conditioning based on fludarabin and busulphan. TCD was performed by adding 20mg alemtuzumab to the graft. Only MA conditioned patients with an UD (n=12) received post transplantation ciclosporin as GvHD prophylaxis, which was tapered from 1 month after alloSCT. Clinically significant GvHD was defined as need of therapeutic systemic immunosuppression (tIS) for GvHD for at least 2 weeks or until death. Bone Marrow (BM) chimerism was measured prior to DLI. Three categories of patient chimerism levels were defined: no patient derived cells (absent), patient derived cells present, but < 5% (low), or ≥ 5% (high). In case of persisting or increasing patient chimerim after pDLI, a second DLI was given at 3-6 months after the first. A multi-state model was designed (Figure 1) with the first DLI (DLI1) as starting state and time. Patients starting tIS after DLI1 transit to the state tIS. Patients who need a second DLI, develop a relapse or die, transit to these respective states. Patients who stay in the state of DLI1 are considered to have a positive outcome. All patients had a follow-up of at least one year after DLI. Numbers in the boxes in Figure 1 represent the number of patients in that state at 1 year after DLI1 and numbers next to the arrows indicate the numbers of patients who made the transition between the two states. Donor type (unrelated versus related), conditioning (NMA versus MA) and patient BM chimerism at time of DLI were included in a Cox model for the transition hazards to investigate their association with the development of GvHD after DLI. For the total group, the cumulative incidence of tIS at 1 year after pDLI was 33% (95% CI 21-45%). Patients with an UD had a hazard ratio (HR) of 1.1 (95% CI 0.4-3.3) of needing tIS after DLI1 compared to patients with a RD. Compared to MA conditioning, NMA conditioned patients had a hazard ratio of 2.1 (95% CI 0.5-8.9) of needing tIS after DLI. They had a HR of 0.2 (95% CI 0.04-0.95) of stopping tIS compared to MA conditioned patients, indicating that DLI after NMA conditioning is associated with more severe GVHD. We hypothesized that this was due to the persistence of patient derived APC. BM chimerism at time of DLI was measured in 47 patients. After NMA and MA conditioning, BM patient chimerism was absent in 14% and 56%, low in 41% and 39%, and high in 45% and 6%, respectively (Fisher's exact test p=0.002 for difference between type of conditioning). Compared to the group without patient chimerism, the low and high patient chimerism group had a HR of 1.9 (95% CI 0.9-4.2) and 3.6 (95% CI 1.7-8.0) of needing tIS after DLI, respectively (Figure 2), demonstrating that the level of patient chimerism is a strong predictor for development of GvHD after DLI, even when taking into account the type of conditioning regimen. Patient BM chimerism at time of pDLI is a strong and independent predictor for the risk of developing GvHD. Dose reduction in case of an UD equalized the GvHD risk compared to a RD. When choosing a T cell dose for pDLI, patient chimerism should be considered a relevant parameter. Disclosures No relevant conflicts of interest to declare.

scholarly journals NOD2 Regulates Hematopoietic Cell Function During Graft-Versus-Host Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2453-2453
Author(s):  
Olaf Penack ◽  
Odette M. Smith ◽  
Nury Yim ◽  
Uttam Rao ◽  
Arnab Ghosh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Experimental Colitis ◽  
Hematopoietic System ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells ◽  
Group B

Abstract Abstract 2453 Poster Board II-430 NOD2 polymorphisms are independent risk factors for Crohn's disease and graft-versus-host disease (GVHD). In Crohn's disease, the pro-inflammatory state resulting from NOD2 mutations have been associated with a loss of anti-bacterial function of enterocytes, such as paneth cells. NOD2 has not been studied in experimental allogeneic bone marrow transplantation (allo-BMT). We studied the role of NOD2 during inflammation in murine models of graft-versus-host disease (GVHD) and in experimental colitis. To investigate the role of NOD2 in regulating GVHD in allo-BMT recipients, we used MHC-matched as well as MHC-disparate allo-BMT models. We first assessed the role of NOD2 deficiency of the allo-BMT donor (either donor T cells or bone marrow) and found no significant impact on the development of GVHD. In contrast, we observed significantly more lethal GVHD in NOD2-/- allo-BMT recipients as compared with WT allo-BMT recipients. We next created chimeric mice, which were NOD2 deficient either in the hematopoietic or non-hematopoietic system. After three months, we performed allo-BMTs (B10BRþB6 and LPþB6) using either WT, NOD2-/- or chimeric recipients. We found that the NOD2 deficiency in the hematopoietic system of the recipient, as opposed to a NOD2 deficiency in the non-hematopoietic system, is responsible for the increased severity of GVHD (Fig. 1A). In NOD2-/- allo-BMT recipients we observed that the absolute number of donor T cells as well as their activation status was significantly increased. Next, we transferred CFSE labeled allogeneic WT T cells to NOD2-/- allo-BMT recipients and found increased proliferation and activation, suggesting that NOD2 plays a role in the regulation of host antigen presenting cells (APCs). We then quantified the expression of activation markers and co-stimulatory molecules on host dendritic cells (DCs): CD40, CD80 and CD86 were significantly up-regulated of on host NOD2-/- DCs as compared with WT DCs during GVHD. To study DC function we selected splenic DCs from WT and NOD2-/- allo-BMT recipients with GVHD and used them as stimulators in mixed leukocyte reactions (MLRs). NOD2-/- DCs had a significantly increased ability to induce proliferation of allogeneic T cells as compared with WT DCs. Finally, we used bone marrow chimeras in an experimental colitis model (which has not been done before) and observed again that NOD2 deficiency in the hematopoietic cells results in increased intestinal inflammation (Figure 1B). We conclude that NOD2 regulates the development of GVHD through its inhibitory effect on host APC function. Fig. 1 (A) NOD2 deficiency of the hematopoietic system aggravatges GVHD. Chemeric mice with NOD2 deficiency either in the hematopoietic system or in the non-hematopoietic system were created by syngeneic BMT (B6 WT → B6 NOD2-/- or B6 NOD2-/→ B6 WT). After 90 days, lethally irradiated (11 Gy) B6 WT versus B6 NOD2-/- versus chemeric allo-BMT recipients were transplanted with 5×106 B10BR TCD-BM or 5×106 LP TCD-BM + 2×106 B10BR T Cells or 3×106 LP T cells. combined date from two independent experiments are shown; n = 16/group. (B) NOD2 deficiency of the hematopoietic system aggravates experimental colitis. First, chemeric mice with NOD2 deficiency either in the hematopoietic system or in the non-hematopoietic system were created by syngeneic BMT (B6 WT→B6 NOD2-/- or B6 NOD2-/-→ B6 WT). After 90 days, TNBS colitis (5 mg TNBS in 50% ethanol) was induced; colons were harvested at day+3 after induction of colitis; combined data from two independent experiments are shown; n=8 / group. Fig. 1. (A) NOD2 deficiency of the hematopoietic system aggravatges GVHD. Chemeric mice with NOD2 deficiency either in the hematopoietic system or in the non-hematopoietic system were created by syngeneic BMT (B6 WT → B6 NOD2-/- or B6 NOD2-/→ B6 WT). After 90 days, lethally irradiated (11 Gy) B6 WT versus B6 NOD2-/- versus chemeric allo-BMT recipients were transplanted with 5×106 B10BR TCD-BM or 5×106 LP TCD-BM + 2×106 B10BR T Cells or 3×106 LP T cells. combined date from two independent experiments are shown; n = 16/group. (B) NOD2 deficiency of the hematopoietic system aggravates experimental colitis. First, chemeric mice with NOD2 deficiency either in the hematopoietic system or in the non-hematopoietic system were created by syngeneic BMT (B6 WT→B6 NOD2-/- or B6 NOD2-/-→ B6 WT). After 90 days, TNBS colitis (5 mg TNBS in 50% ethanol) was induced; colons were harvested at day+3 after induction of colitis; combined data from two independent experiments are shown; n=8 / group. Disclosures: No relevant conflicts of interest to declare.

Irradiated Donor Leukocytes Promote Engraftment of Allogeneic Bone Marrow in Major Histocompatibility Complex Mismatched Recipients Without Causing Graft-Versus-Host Disease

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3222-3233 ◽  
Author(s):  
Edmund K. Waller ◽  
Alan M. Ship ◽  
Stephen Mittelstaedt ◽  
Timothy W. Murray ◽  
Richard Carter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Graft Versus Host Disease ◽  
Graft Rejection ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Histocompatibility Complex ◽  
Donor T Cells

Abstract Graft rejection in allogeneic bone marrow transplantation (BMT) can occur when donor and recipient are mismatched at one or more major histocompatibility complex (MHC) loci. Donor T cells can prevent graft rejection, but may cause fatal graft-versus-host disease (GVHD). We tested whether irradiation of allogeneic donor lymphocytes would preserve their graft-facilitating activity while inhibiting their potential for GVHD. Infusions of irradiated allogeneic T cells did not cause GVHD in MHC-mismatched SJL → (SJL × C57BL6) F1, C57BL6 → B10.RIII, and C57BL6 → B10.BR mouse donor → recipient BMT pairs. The 60-day survival among MHC-mismatched transplant recipients increased from 2% (BM alone) to up to 75% among recipients of BM plus irradiated allogeneic splenocytes. Optimal results were obtained using 50 × 106 to 75 × 106 irradiated donor splenocytes administered in multiple injections from day −1 to day +1. Recipients of an equal number of nonirradiated MHC-mismatched donor splenocytes uniformly died of acute GVHD. The graft facilitating activity of the irradiated allogeneic splenocytes was mediated by donor T cells. Irradiation to 7.5 Gy increased nuclear NFκB in T cells and their allospecific cytotoxicity. Irradiated T cells survived up to 3 days in the BM of MHC-mismatched recipients without proliferation. Recipients of irradiated allogeneic splenocytes and allogeneic BM had stable donor-derived hematopoiesis without a significant representation of donor splenocytes in the T-cell compartment. Irradiated allogeneic T cells thus represent a form of cellular immunotherapy with time-limited biologic activity in vivo that can facilitate allogeneic BMT without causing GVHD.

scholarly journals Prevention of Graft-Versus-Host Disease by Intra-Bone Marrow Injection of Donor T Cells

Stem Cells ◽  
2007 ◽  
Vol 25 (6) ◽  
pp. 1595-1601 ◽  
Author(s):  
Junichi Fukui ◽  
Muneo Inaba ◽  
Yusuke Ueda ◽  
Takashi Miyake ◽  
Naoki Hosaka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells

scholarly journals Interleukin-12 Inhibits Graft-Versus-Host Disease Through an Fas-Mediated Mechanism Associated With Alterations in Donor T-Cell Activation and Expansion

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3315-3322 ◽  
Author(s):  
Bimalangshu R. Dey ◽  
Yong-Guang Yang ◽  
Gregory L. Szot ◽  
Denise A. Pearson ◽  
Megan Sykes
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Interleukin 12 ◽  
Cd4 Cells ◽  
Activation Markers ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells

We have recently made the paradoxical observation that a single injection of recombinant murine interleukin-12 (IL-12) on the day of bone marrow transplantation (BMT) inhibits graft-versus-host disease (GVHD) in lethally irradiated mice receiving fully major histocompatability complex (MHC)-mismatched bone marrow and spleen cells. We have now examined the mechanism of this effect of IL-12 on acute GVHD. By day 4 post-BMT, IL-12–treated mice showed marked reductions in splenic donor CD4+ and CD8+ T cells compared with GVHD controls. Expression of the early activation markers IL-2R alpha chain (CD25) and CD69 on splenic donor CD4+ cells was considerably higher at early time points (36 and 72 hours post-BMT) in IL-12–treated mice compared with GVHD controls. However, the later, GVHD-associated increase in CD25 and very late antigen-4 (VLA-4) expression on donor T cells was greatly depressed in IL-12–protected mice compared with GVHD controls. The marked GVHD-associated expansion of host-reactive T helper cells by day 4 was also completely inhibited in the IL-12–treated group. Expression of Fas was increased on donor CD4 cells of IL-12–treated mice compared with those of controls on days 3 through 7 post-BMT. Furthermore, the ability of IL-12 to protect against GVHD was at least partially dependent on the ability of donor cells to express functional Fas molecules. We conclude that IL-12 treatment at the time of BMT markedly perturbs the activation of alloreactive donor CD4+ T cells that play a critical role in the pathogenesis of acute GVHD. We hypothesize that these perturbations culminate in Fas-dependent apoptosis of donor T cells, thus impeding their expansion and their GVHD-promoting activity.

scholarly journals Role of MMP-13 in Graft-Versus-Host Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1928-1928
Author(s):  
Hui-Hui Ma ◽  
Jing Fu ◽  
Suzanne Lentzsch ◽  
Markus Y Mapara
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Graft Versus Host Disease ◽  
Research Funding ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells

Matrix metalloproteinases (MMPs) have been initially recognized for their role in degradation of extracellular matrix (ECM) and collagen remodeling. However, MMPs have been shown to play a crucial role in inflammation, tumor cell invasion, adaptive and innate immunity. Acute and chronic Graft versus Host Disease (GVHD) are characterized by distinctive histopathological features involving tissue infiltration with donor cells, tissue damage and remodeling. We therefore hypothesized that GVHD-associated organ damage may involve MMPs. We have now identified a novel immunomodulatory function for MMP-13 (alternatively called collagenase-3)and have uncovered a previously unknown role of MMP-13 in regulating GVHD.To address the function of MMP-13 in GVHD we first assesed the effect of MMP-13 on alloresponses in vitro. Using fully Major Histocompatibility Complex (MHC)-mismatched standard mixed lymphocyte reaction we demonstated that antigen presentig cells (APC) from B6.MMP-13-/-(H2b) mice led to signifcantly enhanced antigen-driven activation and proliferation of Carboxyfluorescein succinimidyl ester (CFSE)-labeled Balb/c responder splenocytes. Thus, MMP-13 deficiency in either splenocytes or bone marrow-derived dendritic cells used as stimulators resulted in enhanced proliferation, activation and IFN-gproduction in the allo-reactive lymphocyte responders. Similarly, exogenous MMP13 reduced proliferation of responder T cells as determined tested by CFSEdilution (CFSEloof CD4+T cells from 62.3% decreased to 40.6%, CFSEloof CD8+T cells from 74.1% down to 47.9%). We next assessed the impact of MMP-13 in vivousing fully MHC-mismatched rodent acute GVHD models. To study the role of host-derived MMP-13 we induced GVHD in B6.MMP-13-/-or B6.WT recipient mice following lethal TBI (1075 rad) using splenic T cells from Balb/cdonors. We observed signifcantly accelerated GVHD-related mortality (Median Survival Time 7 vs. 47 days post-transplant, p<0.05) in MMP-13-deficient recipients. Most importantly, donor T cells expanded more vigorously in the secondary lymphoid organs (Spleen and mesenteric lymphnoodes) of MMP13-/-compared to wildtype recipient mice (e.g. spleen: absolute donor CD4+Tcells 1.5x104± 7.3 x 103 (WT) vs. 5.83 x104±1.65 x104[MMP-13-/-] and CD8+5.5 x104± 3.8 x104(WT) vs 3.4 x105±1.4 x105[MMP-13-/-], p<0.01). Enhanced donor lymphocyte expansion was further confirmed by bioluminescence imaging. To further delineate the underlying mechanisms, we analyzed the effects of MMP-13deficiency and exogenous MMP-13 on maturation of mouse bone marrow derived-dendritic cells (BMDC) and macrophages in vitro. We noted decreased expression of inhibitory molecules PD-L1 and PD-1H on GM-CSF/LPS cultured BMDC. Similarly, bone marrow-derived MMP-13-/-macrophages also showed reduced PD-L1 and PD-1H expression upon LPS stimulation when compared to their WT counterparts. In summary we posit that recipient myeloid cell-derived MMP-13 mitigates GVHD and limits donor T cell expansion. Further studies are warranted to determine how MMP-13 suppresses expansion of donor T cells and impacts Graft-versus-Leukemia responses. Disclosures Lentzsch: Caelum Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Clinical Care Options: Speakers Bureau; Sanofi: Consultancy, Research Funding; Multiple Myeloma Research Foundation: Honoraria; International Myeloma Foundation: Honoraria; Karyopharm: Research Funding; Columbia University: Patents & Royalties: 11-1F4mAb as anti-amyloid strategy; Proclara: Consultancy; BMS: Consultancy.

Irradiated Donor Leukocytes Promote Engraftment of Allogeneic Bone Marrow in Major Histocompatibility Complex Mismatched Recipients Without Causing Graft-Versus-Host Disease

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3222-3233 ◽  
Author(s):  
Edmund K. Waller ◽  
Alan M. Ship ◽  
Stephen Mittelstaedt ◽  
Timothy W. Murray ◽  
Richard Carter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Graft Versus Host Disease ◽  
Graft Rejection ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Histocompatibility Complex ◽  
Donor T Cells

Graft rejection in allogeneic bone marrow transplantation (BMT) can occur when donor and recipient are mismatched at one or more major histocompatibility complex (MHC) loci. Donor T cells can prevent graft rejection, but may cause fatal graft-versus-host disease (GVHD). We tested whether irradiation of allogeneic donor lymphocytes would preserve their graft-facilitating activity while inhibiting their potential for GVHD. Infusions of irradiated allogeneic T cells did not cause GVHD in MHC-mismatched SJL → (SJL × C57BL6) F1, C57BL6 → B10.RIII, and C57BL6 → B10.BR mouse donor → recipient BMT pairs. The 60-day survival among MHC-mismatched transplant recipients increased from 2% (BM alone) to up to 75% among recipients of BM plus irradiated allogeneic splenocytes. Optimal results were obtained using 50 × 106 to 75 × 106 irradiated donor splenocytes administered in multiple injections from day −1 to day +1. Recipients of an equal number of nonirradiated MHC-mismatched donor splenocytes uniformly died of acute GVHD. The graft facilitating activity of the irradiated allogeneic splenocytes was mediated by donor T cells. Irradiation to 7.5 Gy increased nuclear NFκB in T cells and their allospecific cytotoxicity. Irradiated T cells survived up to 3 days in the BM of MHC-mismatched recipients without proliferation. Recipients of irradiated allogeneic splenocytes and allogeneic BM had stable donor-derived hematopoiesis without a significant representation of donor splenocytes in the T-cell compartment. Irradiated allogeneic T cells thus represent a form of cellular immunotherapy with time-limited biologic activity in vivo that can facilitate allogeneic BMT without causing GVHD.

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