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Studies on the mechanism and specificity of the effect of the synthetic random copolymer GLAT on graft-versus-host disease.

Publication ,  Journal Article
Aharoni, R; Schlegel, PG; Teitelbaum, D; Roikhel-Karpov, O; Chen, Y; Arnon, R; Sela, M; Chao, NJ
Published in: Immunol Lett
July 1997

Graft-versus-host disease (GVHD), which occurs when donor T-cells recognize multiple minor host histocompatibility antigens as non-self, presents the major limitation to successful allogeneic bone-marrow transplantation. The synthetic random copolymer of the amino acids, L-Glu, L-Lys, L-Ala and L-Tyr, termed GLAT, with promiscuous binding to multiple MHC class II alleles, reduces the incidence, onset and severity of disease in the BIO.D2 --> BALB/c model of lethal GVHD. GLAT inhibited the proliferative response towards host of both spleen cells from mice with GVHD and also of the effector T cell line established from these mice. Administration of GLAT for a limited period after transplantation completely abolished the cytotoxic activity toward host cells exerted by spleen cells from mice with GVHD. Whereas spleen and bone marrow cells from control mice with GVHD secreted IL-2 and INF-gamma when cocultured with host cells, these inflammatory cytokines could not be detected in supernatants of cells from GLAT treated mice. Moreover spleens and bone marrow cells from GLAT treated mice secreted small but significant amounts of IL-4 and IL-6 when cocultured with GLAT, suggesting that GLAT not only inhibits pro-GVHD cytokines but also causes a beneficial effect by inducing secretion of Th2 type cytokines. GLAT binds strongly to MHC molecules of host as well as donor haplotype. D-GLAT, identical to GLAT but composed of D-amino acids is also effective in preventing GVHD. D-GLAT does not cross-react with L-GLAT, but still binds strongly to MHC-class II molecules. These findings indicate that MHC blocking is involved in the therapeutic effect of GLAT on GVHD. The cumulative data demonstrate that GLAT modulates the effector mechanisms involved in GVHD, and can be potentially used for the prevention of GVHD across minor histocompatibility barriers.

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Published In

Immunol Lett

DOI

ISSN

0165-2478

Publication Date

July 1997

Volume

58

Issue

2

Start / End Page

79 / 87

Location

Netherlands

Related Subject Headings

  • Th2 Cells
  • Th1 Cells
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocyte Subsets
  • Spleen
  • Radiation Chimera
  • Polymers
  • Peptides
  • Mice, Inbred Strains
  • Mice, Inbred BALB C
 

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Aharoni, R., Schlegel, P. G., Teitelbaum, D., Roikhel-Karpov, O., Chen, Y., Arnon, R., … Chao, N. J. (1997). Studies on the mechanism and specificity of the effect of the synthetic random copolymer GLAT on graft-versus-host disease. Immunol Lett, 58(2), 79–87. https://doi.org/10.1016/s0165-2478(97)00032-1
Aharoni, R., P. G. Schlegel, D. Teitelbaum, O. Roikhel-Karpov, Y. Chen, R. Arnon, M. Sela, and N. J. Chao. “Studies on the mechanism and specificity of the effect of the synthetic random copolymer GLAT on graft-versus-host disease.Immunol Lett 58, no. 2 (July 1997): 79–87. https://doi.org/10.1016/s0165-2478(97)00032-1.
Aharoni R, Schlegel PG, Teitelbaum D, Roikhel-Karpov O, Chen Y, Arnon R, et al. Studies on the mechanism and specificity of the effect of the synthetic random copolymer GLAT on graft-versus-host disease. Immunol Lett. 1997 Jul;58(2):79–87.
Aharoni, R., et al. “Studies on the mechanism and specificity of the effect of the synthetic random copolymer GLAT on graft-versus-host disease.Immunol Lett, vol. 58, no. 2, July 1997, pp. 79–87. Pubmed, doi:10.1016/s0165-2478(97)00032-1.
Aharoni R, Schlegel PG, Teitelbaum D, Roikhel-Karpov O, Chen Y, Arnon R, Sela M, Chao NJ. Studies on the mechanism and specificity of the effect of the synthetic random copolymer GLAT on graft-versus-host disease. Immunol Lett. 1997 Jul;58(2):79–87.
Journal cover image

Published In

Immunol Lett

DOI

ISSN

0165-2478

Publication Date

July 1997

Volume

58

Issue

2

Start / End Page

79 / 87

Location

Netherlands

Related Subject Headings

  • Th2 Cells
  • Th1 Cells
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocyte Subsets
  • Spleen
  • Radiation Chimera
  • Polymers
  • Peptides
  • Mice, Inbred Strains
  • Mice, Inbred BALB C