Immune Netw.  2011 Dec;11(6):428-430. 10.4110/in.2011.11.6.428.

Anti-CD137 mAb Deletes Both Donor CD4+ and CD8+ T Cells in Acute Graft-versus-host Disease

• Kim J
• Cho HR
• Kwon B

• KMID: 2150732
• DOI: http://doi.org/10.4110/in.2011.11.6.428

Abstract

We previously demonstrated that in vivo engagement of CD137, a member of TNF receptor superfamily, can delete allorective CD4+ T cells through the induction of activation-induced cell death (AICD) in chronic graft-versus-host disease (cGVHD) and subsequently reverse established cGVHD. In this study, we further showed that agonistic anti-CD137 mAb was highly effective in triggering AICD of donor CD8+ T cells as well as donor CD4+ T cells in the C57BL/6-->unirradiated (C57BL/6 x DBA/2)F1 acute GVHD model. Our results suggest that strong allostimulation should facilitate AICD of both alloreactive CD4+ and CD8+ T cells induced by CD137 stimulation. Therefore, depletion of pathogenic T cells using agonistic anti-CD137 mAb combined with potent TCR stimulation may be used to block autoimmune or inflammatory diseases mediated by T cells.

Keyword

Rodent; T cells; Graft versus host disease; Costimulation

MeSH Terms

Cell Death
Graft vs Host Disease
Humans
Receptors, Tumor Necrosis Factor
Rodentia
T-Lymphocytes
Tissue Donors
Receptors, Tumor Necrosis Factor

Figure

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  Figure 1 Anti-CD137 mAb induces apoptosis of both donor CD4+ and CD8+ T cells in aGVHD. aGVHD was induced by transferring 5×107 C57BL/6 spleen/lymph node cells into BDF1 mice. Immediately thereafter, anti-CD137 mAb or control Ig (200µg per mouse) was injected. Splenocytes were analyzed by flow cytometry 5 days after parental cell transfer. (A) Percent of Annexin V+ donor CD4+ and CD8+ T cells. (B) Percent of CD62Llow donor CD4+ and CD8+ T cells. n=3 mice per group. *p<0.01 and ***p<0.001 between the 2 groups.

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  Figure 2 Anti-CD137 mAb completely blocks aGVHD. aGVHD was induced by transferring 5×107 C57BL/6 spleen/lymph node cells into BDF1 mice. Immediately thereafter, anti-CD137 mAb or control Ig (200µg per mouse) was injected (n=10 per group). (A) Changes of body weight. *p<0.05 and ***p<0.001 between the 2 groups at the indicated time points. (B) Survival curve. **p<0.05 between the 2 groups.

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