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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0176.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2650-2658
TRANSPLANTATION
Cytokine and chemokine profiles in autologous graft-versus-host
disease (GVHD): interleukin 10 and interferon  may be critical
mediators for the development of autologous GVHD
Yuji Miura,
Christopher J. Thoburn,
Emilie C. Bright,
Weiran Chen,
Shinji Nakao, and
Allan D. Hess
From the Johns Hopkins University School of Medicine,
Oncology Center and the Kanazawa University Graduate School of Medical
Science, Cellular Transplantation Biology.
Administration of the immunosuppressive drug cyclosporine A (CsA)
following autologous stem cell transplantation paradoxically elicits a
systemic autoimmune syndrome resembling graft-versus-host disease
(GVHD). This syndrome, termed autologous GVHD, is associated with
autoreactive CD8+ T cells that recognize major
histocompatibility complex (MHC) class II determinants in association
with a peptide from the invariant chain. To investigate the potential
role of cytokines and chemokines in autologous GVHD, interleukin 2 (IL-2), IL-4, IL-10, interferon  (IFN-), and macrophage
inflammatory protein-1 (MIP-1) gene expression in peripheral
blood mononuclear cells (PBMCs) was determined in 36 patients
treated with CsA following transplantation and correlated with the
induction of cytolytic activity against autologous phytohemagglutinin-stimulated lymphocytes (PHA-blasts) and the breast
cancer cell line (T47D). The determination of gene expression by
real-time polymerase chain reaction (PCR) revealed that IL-10 mRNA
levels by PBMCs in patients with autologous GVHD were 29-fold higher
than in healthy individuals. IFN- (4-fold), IL-2 (3-fold), and
MIP-1 (44-fold) mRNA levels were also increased in GVHD-induced patients compared with healthy individuals. The ability of PBMCs to
lyse autologous PHA-blasts and T47D tumor cells exhibited an identical
temporal relationship with expression of IL-10 and IFN- during
autologous GVHD. Moreover, the susceptibility to autologous GVHD as
assessed in 75 patients was significantly associated with the
IL-10 1082 G/G polymorphic alleles, allelic variants in
the promoter region that govern IL-10 production. These findings
indicate that IL-10 may play an unexpected but critical role in
autologous GVHD and could be utilized to enhance a graft-versus-tumor
effect after transplantation. Interestingly, polymorphisms in the IL-10
promoter region may also explain differences in the susceptibility of
patients to autologous GVHD induction.
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