Chloroquine treatment affects T-cell priming to minor histocompatibility
antigens and graft-versus-host disease
KR Schultz, S Bader, J Paquet and W Li
Department of Pediatrics, University of British Columbia, Vancouver,
Canada.
Graft-versus-host disease (GVHD) caused by T-cell recognition of minor
histocompatibility (MiHC) antigens is a major complication of bone marrow
transplantation. GVHD therapy has focused on removal or suppression of
donor T cells, but modulation of MiHC antigen presentation to CD4+ T cells
may represent an alternative approach. Chloroquine is known to inhibit
major histocompatibility complex (MHC) class II presentation of antigen in
vitro by affecting invariant chain dissociation from MHC class II. The goal
of this study was to evaluate the role of chloroquine in abrogating T-cell
priming to MiHC and GVHD in mice after transplantation of an MiHC
incompatible donor. C57BL/6 mice were treated with phosphate-buffered
saline or chloroquine at 400 micrograms intraperitoneally every day for 5
days before priming with BALB.B cells (MiHC-incompatible) followed by
weekly injections of chloroquine at 400 micrograms for 4 to 8 weeks.
Chloroquine treatment decreased the proliferative T-cell response to MiHC
by 67% and the cytolytic T-cell activation by greater than 50%. After bone
marrow transplantation (LP/J into C57BL/6; MiHC-incompatible), GVHD was
significantly decreased in chloroquine-treated mice (17% with GVHD) as
compared with that in controls (92% with GVHD). Chloroquine treatment did
not have other effects in vivo on the normal T- and B-cell mitogenic
responses, T-cell allogeneic responses, and MHC class II and I surface
expression. Chloroquine treatment does decrease the ability of C57BL/6
antigen-presenting cells to stimulate C3H.SW T cells reactive with MiHC
expressed on C57BL/6 cells, suggesting an effect on MHC class II
presentation of MiHC in vivo. Treatment with chloroquine in vivo appears to
result in decreased CD4+ T-cell priming to MiHC and GVHD by decreased class
II MHC antigen presentation. Thus, chloroquine treatment may represent an
alternative approach to control GVHD.
Volume 86,
Issue 11,
pp. 4344-4352,
12/01/1995
Copyright © 1995 by The American Society of Hematology
