Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 109, Issue 4, Pages 549-557Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI200213604
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Funding
- NCI NIH HHS [CA-79915, R01 CA085721, CA85721] Funding Source: Medline
- NHLBI NIH HHS [R01 HL056067, R37 HL056067, HL-56067] Funding Source: Medline
- NIAID NIH HHS [R01 AI034495, AI-35225, AI-34495] Funding Source: Medline
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Previous studies have shown that blockade of LIGHT, a T cell costimulatory molecule belonging to the TNF superfamily, by soluble lymphotoxin beta receptor-Ig (LTbetaR-Ig) inhibits the cytotoxic T lymphocyte (CTL) response to host antigenic disparities and ameliorates lethal graft-versus-host disease (GVHD) in a B6 to BDF1 mouse model. Here, we demonstrate that infusion of an mAb against CD40 ligand (CD40L) further increases the efficacy of LTbetaR-Ig, leading to complete prevention of GVHD. We further demonstrate that alloantigen-specific CTLs become anergic upon rapid expansion, and persist in the tolerized mice as a result of costimulatory blockade. Transfer of anergic CTLs to secondary F1 mice fails to induce GVHD despite the fact that anergic CTLs can be stimulated to proliferate in vitro by antigens and cytokines. Our study provides a potential new approach for the prevention of lethal GVHD.
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