Send to:

Choose Destination
See comment in PubMed Commons below
Blood. 2008 Apr 1;111(7):3884-92. doi: 10.1182/blood-2007-11-125294. Epub 2008 Jan 25.

CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL.

Author information

  • 1Section of Medical Oncology, Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8032, USA.


Whether T-cell antigen receptors (TCR) on donor T cells require direct interactions with major histocompatibility complex class I or class II (MHCI/MHCII) molecules on target cells to mediate graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) is a fundamental question in allogeneic stem-cell transplantation (alloSCT). In MHC-mismatched mouse models, these contacts were not required for GVHD. However, this conclusion may not apply to MHC-matched, multiple minor histocompatibility antigen-mismatched alloSCT, the most common type performed clinically. To address this, we used wild-type (wt)-->MHCI-/- or wt-->MHCII-/- bone marrow chimeras as recipients in GVHD experiments. For GVL experiments, we used MHCI-/- or MHCII-/- chronic-phase CML cells created by expressing the BCR-ABL cDNA in bone marrow from MHCI-/- or MHCII-/- mice. TCR/MHCI contact was obligatory for both CD8-mediated GVHD and GVL. In contrast, CD4 cells induced GVHD in wt-->MHCII-/- chimeras, whereas MHCII-/- mCP-CML was GVL-resistant. Donor CD4 cells infiltrated affected skin and bowel in wt-->MHCII-/- recipients, indicating that they mediated GVHD by acting locally. Thus, CD4 cells use distinct effector mechanisms in GVHD and GVL: direct cytolytic action is required for GVL but not for GVHD. If these noncytolytic pathways can be inhibited, then GVHD might be ameliorated while preserving GVL.

[PubMed - indexed for MEDLINE]
Free PMC Article

LinkOut - more resources

Full Text Sources

Other Literature Sources


Molecular Biology Databases

Research Materials


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk