cd40 antigens


Summary: Members of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. They are found on mature B-LYMPHOCYTES, some EPITHELIAL CELLS; and lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.

Top Publications

  1. Lievens D, Eijgelaar W, Biessen E, Daemen M, Lutgens E. The multi-functionality of CD40L and its receptor CD40 in atherosclerosis. Thromb Haemost. 2009;102:206-14 pubmed publisher
    ..In this review, we highlight the cell-type specific multi-functionality of CD40-CD40L signalling in atherosclerosis. ..
  2. Iezzi G, Sonderegger I, Ampenberger F, Schmitz N, Marsland B, Kopf M. CD40-CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4+ T cells. Proc Natl Acad Sci U S A. 2009;106:876-81 pubmed publisher
    ..Our data demonstrate that CD40-CD40L cross-talk is important for Th17 development by translating strong T cell receptor and microbial stimuli into IL-6 production. ..
  3. Zheng X, Vladau C, Zhang X, Suzuki M, Ichim T, Zhang Z, et al. A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation. Blood. 2009;113:2646-54 pubmed publisher
    ..In conclusion, this is the first demonstration of DC-specific siRNA delivery and gene silencing in vivo, which highlights the potential of DC-mediated immune modulation and the feasibility of siRNA-based clinical therapy. ..
  4. Law C, Grewal I. Therapeutic interventions targeting CD40L (CD154) and CD40: the opportunities and challenges. Adv Exp Med Biol. 2009;647:8-36 pubmed publisher
    ..This chapter reviews the role of CD40-CD40L costimulation in disease pathogenesis, the characteristics of therapeutic agents targeting this pathway and status of their clinical development. ..
  5. Zheng J, Liu Y, Lau Y, Tu W. CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells. Cell Mol Immunol. 2010;7:44-50 pubmed publisher
    ..Additionally, using CD40-B to generate Tregs may accelerate the clinical use of Treg-based immunotherapy in the treatment of allograft rejection, graft versus host disease (GVHD) and autoimmune diseases. ..
  6. Raychaudhuri S, Remmers E, Lee A, Hackett R, Guiducci C, Burtt N, et al. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet. 2008;40:1216-23 pubmed publisher
    ..1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall). ..
  7. Li L, Wang H, Wang B. Anergic cells generated by blocking CD28 and CD40 costimulatory pathways in vitro ameliorate collagen induced arthritis. Cell Immunol. 2008;254:39-45 pubmed publisher
    ..This effective treatment is associated with a reduction in IFN-gamma production and through cell-cell contact. Our results suggest that anergic cells may be beneficial for the treatment of rheumatoid arthritis. ..
  8. Pilon C, Levast B, Meurens F, Le Vern Y, Kerboeuf D, Salmon H, et al. CD40 engagement strongly induces CD25 expression on porcine dendritic cells and polarizes the T cell immune response toward Th1. Mol Immunol. 2009;46:437-47 pubmed publisher
    ..This study therefore underlines that the nature of the stimulus strongly influences the capacity of DC to steer the immune response in the pig. ..
  9. Portillo J, Van Grol J, Zheng L, Okenka G, Gentil K, Garland A, et al. CD40 mediates retinal inflammation and neurovascular degeneration. J Immunol. 2008;181:8719-26 pubmed

More Information


  1. Weiss J, Back T, Scarzello A, Subleski J, Hall V, Stauffer J, et al. Successful immunotherapy with IL-2/anti-CD40 induces the chemokine-mediated mitigation of an immunosuppressive tumor microenvironment. Proc Natl Acad Sci U S A. 2009;106:19455-60 pubmed publisher
    ..These results suggest that the use of anti-CD40 in combination with IL-2 or IL-15 may hold substantially more promise for clinical cancer treatment than anti-CD40 alone. ..
  2. Matsuzawa A, Tseng P, Vallabhapurapu S, Luo J, Zhang W, Wang H, et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science. 2008;321:663-8 pubmed publisher
    ..This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling. ..
  3. Dasu T, Sindhava V, Clarke S, Bondada S. CD19 signaling is impaired in murine peritoneal and splenic B-1 B lymphocytes. Mol Immunol. 2009;46:2655-65 pubmed publisher
    ..These findings suggest a defect in CD19-mediated signals in both peritoneal and splenic B-1 B lymphocytes, which is in part, due to higher levels of constitutively active Lyn. ..
  4. Peters A, Stunz L, Bishop G. CD40 and autoimmunity: the dark side of a great activator. Semin Immunol. 2009;21:293-300 pubmed publisher
    ..This review discusses the role of CD40:CD154 interaction in human and mouse autoimmunity, human polymorphisms associated with disease incidence, and disrupting CD40:CD154 interactions as an autoimmune therapy. ..
  5. Engel D, Seijkens T, Poggi M, Sanati M, Thevissen L, Beckers L, et al. The immunobiology of CD154-CD40-TRAF interactions in atherosclerosis. Semin Immunol. 2009;21:308-12 pubmed publisher
    ..Its cell-type specific actions, signal transduction cascades and its therapeutic potentials will be discussed. ..
  6. Zheng J, Liu Y, Qin G, Chan P, Mao H, Lam K, et al. Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells. J Immunol. 2009;183:3742-50 pubmed publisher
    ..This approach may facilitate the clinical application of CD8(+) Treg-based immunotherapy in transplantation and autoimmune diseases. ..
  7. Bishop G, Xie P. Multiple roles of TRAF3 signaling in lymphocyte function. Immunol Res. 2007;39:22-32 pubmed
    ..TRAF3 is also important for signaling via innate immune receptors, as well as an oncogenic mimic of a normal receptor that is implicated in promoting both malignancies and autoimmunity. ..
  8. Suzuki M, Zheng X, Zhang X, Li M, Vladau C, Ichim T, et al. Novel vaccination for allergy through gene silencing of CD40 using small interfering RNA. J Immunol. 2008;180:8461-9 pubmed
    ..The present study highlights a therapeutic potential of siRNA-based treatment for allergic diseases. ..
  9. Alderson K, Zhou Q, Berner V, Wilkins D, Weiss J, Blazar B, et al. Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy. J Immunol. 2008;180:2981-8 pubmed
    ..These results suggest that subset-specific expansion may contribute to marked shifts in the composition of the T cell compartment, potentially influencing the effectiveness of some immunotherapeutic approaches that rely on IFN-gamma. ..
  10. Donners M, Beckers L, Lievens D, Munnix I, Heemskerk J, Janssen B, et al. The CD40-TRAF6 axis is the key regulator of the CD40/CD40L system in neointima formation and arterial remodeling. Blood. 2008;111:4596-604 pubmed publisher
    ..This identifies the CD40-TRAF6 axis as a potential therapeutic target in vascular disease. ..
  11. Hostager B. Roles of TRAF6 in CD40 signaling. Immunol Res. 2007;39:105-14 pubmed
  12. t Hart B, Hintzen R, Laman J. Preclinical assessment of therapeutic antibodies against human CD40 and human interleukin-12/23p40 in a nonhuman primate model of multiple sclerosis. Neurodegener Dis. 2008;5:38-52 pubmed
    ..The promising effects during ongoing disease in a relevant preclinical IMID model illustrate the potential of these two antibodies as treatment of IMID, in particular for multiple sclerosis on which disease EAE has been modeled. ..
  13. Ahonen C, Wasiuk A, Fuse S, Turk M, Ernstoff M, Suriawinata A, et al. Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines. Blood. 2008;111:3116-25 pubmed publisher
    ..These findings provide intelligent strategies for the formulation of multifactorial vaccines to achieve maximal efficacy in cancer vaccine trials in humans. ..
  14. Xu W, Santini P, Matthews A, Chiu A, Plebani A, He B, et al. Viral double-stranded RNA triggers Ig class switching by activating upper respiratory mucosa B cells through an innate TLR3 pathway involving BAFF. J Immunol. 2008;181:276-87 pubmed
  15. Guerreiro Cacais A, Levitskaya J, Levitsky V. B cell receptor triggering sensitizes human B cells to TRAIL-induced apoptosis. J Leukoc Biol. 2010;88:937-45 pubmed publisher
    ..This may be important for our understanding of TRAIL involvement in the control of B cell responses and aid in designing TRAIL-based therapies for B cell lymphomas...
  16. Carreno B, Becker Hapak M, Linette G. CD40 regulates human dendritic cell-derived IL-7 production that, in turn, contributes to CD8(+) T-cell antigen-specific expansion. Immunol Cell Biol. 2009;87:167-77 pubmed publisher
    ..These results show that CD40 signals regulate DC-derived IL-7 production that, in turn, may instruct CD8(+) T cells at the time of TCR engagement for survival leading to an increased expansion of antigen-specific T cells. ..
  17. Baruah P, Dumitriu I, Malik T, Cook H, Dyson J, Scott D, et al. C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells. Blood. 2009;113:3485-93 pubmed publisher
    ..Our novel data suggest that C1q augments the production of IL-12p70 by mouse and human DCs after CD40 triggering and plays important roles in sustaining the maturation of DCs and guiding the activation of T cells. ..
  18. Sibarani R. Genetics of Graves' disease: the lost concept. Acta Med Indones. 2009;41:37-40 pubmed
    ..The importance of the environment with the mechanisms involved including genetic factors is needed to be decided. ..
  19. Hsiao J, Hsieh M, Hsiao C, Weng H, Ke D. Association of CD40 and thyroglobulin genes with later-onset Graves' disease in Taiwanese patients. Eur J Endocrinol. 2008;159:617-21 pubmed publisher
    ..These data suggest that the T/T genotype and T allele in the CD40 gene are more likely to be associated with late-onset GD in Taiwanese patients. ..
  20. Godoy L, Moretti A, Jurado M, Oxer D, Janiszewski M, Ckless K, et al. Loss of CD40 endogenous S-nitrosylation during inflammatory response in endotoxemic mice and patients with sepsis. Shock. 2010;33:626-33 pubmed publisher
    ..Our results support a novel post-translational regulatory mechanism in which the CD40 signal may be, at least in part, dependent on cellular activation-induced receptor denitrosylation. ..
  21. De Gonzalo Calvo D, Llorente Cortes V, Orbe J, Paramo J, Badimon L. Altered atherosclerotic-related gene expression signature in circulating mononuclear leukocytes from hypercholesterolemic patients with low HDL cholesterol levels. Int J Cardiol. 2014;173:337-8 pubmed publisher
  22. Shen X, Wang Y, Gao F, Ren F, Busuttil R, Kupiec Weglinski J, et al. CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia/reperfusion injury. Hepatology. 2009;50:1537-46 pubmed publisher
  23. Liu Z, Zhang J, Lin P, Wang X, Wang Q. [Primary study on preparation and efficiency of neotype hepatocellular carcinoma-dendritic cell vaccine with SOCS1 expression inhibited]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2008;39:177-80 pubmed
    ..Inhibiting SOCS1 can improve the maturation of hepatocellular carcinoma-DC vaccine cell and can increase its inducing ability of anti-cancer immune response. ..
  24. Pearson S, Lancrin C, Lacaud G, Kouskoff V. The sequential expression of CD40 and Icam2 defines progressive steps in the formation of blood precursors from the mesoderm germ layer. Stem Cells. 2010;28:1089-98 pubmed publisher
    ..Taken together, our data identify novel cell surface markers allowing us to further refine our understanding of the events marking progressive hematopoietic commitment from the mesoderm germ layer. ..
  25. Bam M, Bagchi T. Absence of tyrosinase-related protein-2/dopachrome tautomerase transcripts in PBMCs from vitiligo patients. Scand J Immunol. 2009;69:366-73 pubmed publisher
    ..Thus, we conclude that the antigen presenting cells (APC) are not in an activated state and that constitutively activated APC are possibly not required for the progression of the disease once it has been initiated. ..
  26. Neubauer H, Setiadi P, Günesdogan B, Pinto A, Borgel J, Mugge A. Influence of glycaemic control on platelet bound CD40-CD40L system, P-selectin and soluble CD40 ligand in Type 2 diabetes. Diabet Med. 2010;27:384-90 pubmed publisher
    ..Improved glycaemic control, however, does help to correct abnormal platelet activation via down-regulation of CD40-CD40L system and P-selectin expression. ..
  27. Heidt S, Roelen D, Eijsink C, van Kooten C, Claas F, Mulder A. Effects of immunosuppressive drugs on purified human B cells: evidence supporting the use of MMF and rapamycin. Transplantation. 2008;86:1292-300 pubmed publisher
    ..Our data show that MPA and rapamycin are capable of strongly inhibiting B cells responses. This provides a rationale for the use of both MPA and rapamycin to prevent or counteract humoral responses. ..
  28. Dormond O, Contreras A, Meijer E, Datta D, Flynn E, Pal S, et al. CD40-induced signaling in human endothelial cells results in mTORC2- and Akt-dependent expression of vascular endothelial growth factor in vitro and in vivo. J Immunol. 2008;181:8088-95 pubmed
    ..Together, these observations indicate that mTORC2 and Akt facilitate CD40-inducible expression of VEGF in EC, which is of clinical importance in tumor growth and the progression of chronic inflammatory diseases. ..
  29. Reeves R, Wei Q, Stallworth J, Fultz P. Systemic dendritic cell mobilization associated with administration of FLT3 ligand to SIV- and SHIV-infected macaques. AIDS Res Hum Retroviruses. 2009;25:1313-28 pubmed publisher
  30. Nesbeth Y, Martinez D, Toraya S, Scarlett U, Cubillos Ruiz J, Rutkowski M, et al. CD4+ T cells elicit host immune responses to MHC class II-negative ovarian cancer through CCL5 secretion and CD40-mediated licensing of dendritic cells. J Immunol. 2010;184:5654-62 pubmed publisher
  31. Ishiura N, Nakashima H, Watanabe R, Kuwano Y, Adachi T, Takahashi Y, et al. Differential phosphorylation of functional tyrosines in CD19 modulates B-lymphocyte activation. Eur J Immunol. 2010;40:1192-204 pubmed publisher
    ..Thus, variations in phosphorylation patterns may contribute to the complexity of CD19-regulated signal transduction. ..
  32. Suzuki M, Zheng X, Zhang X, Ichim T, Sun H, Kubo N, et al. Inhibition of allergic responses by CD40 gene silencing. Allergy. 2009;64:387-97 pubmed publisher
    ..The present study demonstrates a novel therapeutic use for siRNA in allergy. CD40 siRNA attenuated allergy through inhibition of DC and B cell functions and generation of regulatory T (Treg) cells. ..
  33. Zhang X, Kedl R, Xiang J. CD40 ligation converts TGF-beta-secreting tolerogenic CD4-8- dendritic cells into IL-12-secreting immunogenic ones. Biochem Biophys Res Commun. 2009;379:954-8 pubmed publisher
    ..Therefore, our data provide new information for and may thus have useful impacts in CD40 ligation-based immunotherapy of cancer. ..
  34. Hanafi L, Bolduc M, Gagné M, Dufour F, Langelier Y, Boulassel M, et al. Two distinct chimeric potexviruses share antigenic cross-presentation properties of MHC class I epitopes. Vaccine. 2010;28:5617-26 pubmed publisher
    ..Results suggest that potexvirus VLPs are an attractive vaccine platform for inducing a CTL response. ..
  35. Smulski C, Decossas M, Chekkat N, Beyrath J, Willen L, Guichard G, et al. Hetero-oligomerization between the TNF receptor superfamily members CD40, Fas and TRAILR2 modulate CD40 signalling. Cell Death Dis. 2017;8:e2601 pubmed publisher
    ..Altogether, these data reveal that selective interactions between different TNFRSF members may modulate ligand-induced responses upstream signalling events. ..
  36. Lunde L, Skare Ø, Aass H, Mamen A, Einarsdóttir E, Ulvestad B, et al. Physical activity initiated by employer induces improvements in a novel set of biomarkers of inflammation: an 8-week follow-up study. Eur J Appl Physiol. 2017;117:521-532 pubmed publisher
    ..Exercising several times a week was associated with less inflammation compared to exercising once a week or less. During the 8-week follow-up, total levels of biomarkers of inflammation improved. ..
  37. Qu Q, Ge Y, Chen Y, Chen C, Qiu Y, Zhang X. Preparation and characterization of a novel chimeric antibody against human CD40 with the potential to inhibit Daudi cell proliferation. Hybridoma (Larchmt). 2009;28:121-8 pubmed publisher
    ..This chimeric antibody retained reactivity to human CD40. In vitro, ch-5C11 could effectively inhibit B lymphoma Daudi cell proliferation, suggesting that it might have the potential to be developed for future clinical use. ..
  38. Takahashi H, Mori S, Liu K, Wake H, Zhang J, Liu R, et al. Beta2-adrenoceptor stimulation inhibits advanced glycation end products-induced adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells. Eur J Pharmacol. 2010;627:313-7 pubmed publisher
  39. Ma D, Clark E. The role of CD40 and CD154/CD40L in dendritic cells. Semin Immunol. 2009;21:265-72 pubmed publisher
    ..As research into DC vaccines and immunotherapies progresses, further understanding of CD40 and DC function will advance the applicability of DCs in immunotherapy for human diseases. ..
  40. Johnson S, Zhan Y, Sutherland R, Mount A, Bedoui S, Brady J, et al. Selected Toll-like receptor ligands and viruses promote helper-independent cytotoxic T cell priming by upregulating CD40L on dendritic cells. Immunity. 2009;30:218-27 pubmed publisher
    ..Thus, CD40L upregulation on DCs promoted optimal priming of CD8(+) T cells without CD4(+) T cells, providing a mechanism by which pathogens may elicit helper-independent CTL immunity. ..
  41. Kobayashi S, Haruo N, Sugane K, Ochs H, Agematsu K. Interleukin-21 stimulates B-cell immunoglobulin E synthesis in human beings concomitantly with activation-induced cytidine deaminase expression and differentiation into plasma cells. Hum Immunol. 2009;70:35-40 pubmed publisher
    ..Our data suggest that IL-21 plays an important role in occurrence and the treatment of allergic disorders. ..
  42. Janelsins B, Mathers A, Tkacheva O, Erdos G, Shufesky W, Morelli A, et al. Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity. Blood. 2009;113:3017-26 pubmed publisher
    ..Our results contribute to the understanding of the interactions between the immune and nervous systems that control DC function and present a novel approach for ex vivo-generation of potent immune-stimulatory DCs. ..
  43. Missiou A, Wolf D, Platzer I, Ernst S, Walter C, Rudolf P, et al. CD40L induces inflammation and adipogenesis in adipose cells--a potential link between metabolic and cardiovascular disease. Thromb Haemost. 2010;103:788-96 pubmed publisher
    ..Our data reveal potent metabolic functions of CD40L aside from its known pivotal pro-inflammatory role within plaques. Our data suggest that CD40L may mediate risk at the interface of metabolic and atherothrombotic disease. ..
  44. Gandhi K, McKay F, Cox M, Riveros C, Armstrong N, Heard R, et al. The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis. Hum Mol Genet. 2010;19:2134-43 pubmed publisher
    ..Overall, these data indicate dysregulation of T cells can be detected in the whole blood of untreated MS patients, and supports targeting of activated T cells in therapy for all forms of MS. ..
  45. Suzuki M, Zheng X, Zhang X, Zhang Z, Ichim T, Sun H, et al. A novel allergen-specific therapy for allergy using CD40-silenced dendritic cells. J Allergy Clin Immunol. 2010;125:737-43, 743.e1-743.e6 pubmed publisher
    ..This study is the first to demonstrate a novel allergen-specific therapy for allergy through DC-mediated immune modulation after gene silencing of CD40. ..
  46. Neubauer H, Setiadi P, Pinto A, Günesdogan B, Meves S, Borgel J, et al. Upregulation of platelet CD40, CD40 ligand (CD40L) and P-Selectin expression in cigarette smokers: a flow cytometry study. Blood Coagul Fibrinolysis. 2009;20:694-8 pubmed publisher
    ..These findings emphasize that cigarette smoking leads to a proinflammatory and prothrombotic state thus contributing to accelerated atherosclerosis. ..
  47. Futagami S, Hiratsuka T, Shindo T, Hamamoto T, Horie A, Ueki N, et al. Extracellular HSP70 blocks CD40L-induced apoptosis and tubular formation in endothelial cells. J Gastroenterol Hepatol. 2008;23 Suppl 2:S222-8 pubmed publisher
    ..Extracellular HSP70 treatment blocks CD40L inhibition of apoptosis and CD40L induction of tubular formation in HUVEC. ..
  48. Lapteva N. Enhanced migration of human dendritic cells expressing inducible CD40. Methods Mol Biol. 2010;651:79-87 pubmed publisher
    ..This result suggests that the use of iCD40-modified and LPS-stimulated DCs is a potent strategy in DC-based cancer immunotherapies. ..
  49. Bereznaya N, Kirnasovskaya E, Vinnichuk Y, Belova O, Lukyanova N. Expression of CD40 by the cells of benign and malignant breast tumors and antitumor action of autologous lymphocytes against chemoresistant and chemosensitive tumors. Exp Oncol. 2008;30:295-9 pubmed
    ..Marked antitumor activity of LAK from the patients with drug resistant breast cancer is associated with high expression level of CD40 on tumor cells and with its decreased expression on lymphocytes. ..
  50. Peters A, Stunz L, Meyerholz D, Mohan C, Bishop G. Latent membrane protein 1, the EBV-encoded oncogenic mimic of CD40, accelerates autoimmunity in B6.Sle1 mice. J Immunol. 2010;185:4053-62 pubmed publisher
    ..Sle3 background. These data indicate that LMP1-induced effects can cooperate with distinct subsets of host genes that predispose to autoimmunity and can thus be an exacerbating factor in autoimmune disease via multiple mechanisms. ..
  51. Zhao Q, Kim T, Pang J, Sun W, Yang X, Wang J, et al. A novel function of CXCL10 in mediating monocyte production of proinflammatory cytokines. J Leukoc Biol. 2017;102:1271-1280 pubmed publisher
    ..Targeting CXCL10 is therefore an attractive approach to treating inflammatory diseases that are driven by innate and adaptive immunity. ..
  52. Ng S, Plamondon S, Kamm M, Hart A, Al Hassi H, Guenther T, et al. Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis. Inflamm Bowel Dis. 2010;16:1286-98 pubmed publisher
    ..These effects may contribute to therapeutic benefit. ..
  53. Kim J, Park K, Kim H, Kim J, Kim H, Jung D, et al. Breaking of CD8+ T cell tolerance through in vivo ligation of CD40 results in inhibition of chronic graft-versus-host disease and complete donor cell engraftment. J Immunol. 2008;181:7380-9 pubmed
    ..Taken together, our results suggest that a different intensity of donor CTL activity is required for removal of host hematopoietic cells, including leukemia vs induction of acute GVHD. ..