Abstract
To study the effect of immunologic stimuli on renal expression of Ia antigens (the class II products of the major histocompatibility complex), we induced acute graft-vs-host disease (GVHD) in mice and assessed Ia expression in the host kidney. Serologic absorption analyses showed that the amount of host Ia antigen increased up to tenfold in kidney, and immunofluorescence demonstrated that this increase occurred predominantly in renal tubule epithelial cells. To determine whether these alterations reflected changes in Ia gene transcription, we hybridized DNA probes for mRNAs encoding either Ia Eα or A β chains to total RNA extracted from the kidneys of normal mice and mice with acute GVHD. Northern hybridization blots revealed that the level of Ia mRNA expression in GVHD kidney is enhanced about sevenfold when compared with that found in normal kidney. Using the E α probe, this result was shown to reflect increased expression of C3H host E k α mRNA, since the E b α gene is not transcribed by the C57BL/6 donor strain used. We conclude that the increase in expression of Ia in renal tubule epithelium during GVHD probably reflects increased I-region gene transcription in host kidney cells. These findings may have implications for the pathogenesis of renal allograft rejection and immunologic renal disease.
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Barclay, A. N. and Mason, D. W.: Induction of Ia antigen in rat epithelium by immunological stimuli. J. Exp. Med. 156: 1665–1676, 1982
Beller, D.I. and Ho, K.: Regulation of macrophage populations. V. Evaluation of the control of macrophage la expression in vitro. J. Immunol. 129: 971–976, 1982
Daynes, R. A., Emam, M., Krueger, G. G., and Roberts, L. K.: Expression of Ia antigen on epidermal keratinocytes after the grafting of normal skin to nude mice. J. Immunol. 130: 1536–1539, 1983
Delovitch, T. L., Harris, J. F., Battistella, R., and Kaufman, K.: Role of la antigens in graft vs host reactions. II. Molecular and functional analysis of T cell alloreactivity by the characterization of host la antigens on alloactivated donor T cells. J. Exp. Med. 155: 61–82, 1982
deWaal, R. M. W., Bogman, M. J. J., Maass, C. N., Cornelissen, L. M. H., Tax, W. J. M., and Kocne, R. A. P.: Variable expression of la antigens on the vascular endothelium of mouse skin allografts. Nature 303: 426–429, 1983
Hood, L., Steinmetz, M., and Malissen, B.: Genes of the major histocompatibility complex of the mouse. Annu. Rev. Immunol. 1: 529–568, 1983
Kelley, V. E. and Roths, J. B.: Increase in macrophage Ia expression in autoimmune mice: Role of the 1pr gene. J. Immunol. 129: 923–925, 1982
Lampert, I. A., Suitters, A. J., and Chisholm, P. M.: Expression of Ia antigen on epidermal keratinocytes in graft-versus-host disease. Nature 293: 149–150, 1981
Maniatis, T., Fritsch, E. F., and Sambrook, J.: Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1982
Mayrhofer, G. and Schon-Hegrad, M. A.: Ia antigens in rat kidney, with special reference to their expression in tubular epithelium. J. Exp. Med. 157: 2097–2109, 1983
McIntyre, K. R. and Seidman, J. G.: Nucleotide sequence of mutant I-A bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature 308: 552–553, 1984
McNicholas, J. M., Steinmetz, M., Hunkapiller, T., Jones, P., and Hood, L.: DNA sequence of the gene encoding the E alpha Ia polypeptide of the BALB/c mouse. Science 218: 1229–1232, 1982
Pober, J. S. and Gimbrone, M. A.: Expression of la-like antigens by human vascular endothelial cells is inducible in vitro: Demonstration by monoclonal antibody binding and immunoprecipitation. Proc. Natl. Acad. Sci. U.S.A. 79: 6641–6645, 1982
Pober, J. S., Gimbrone, M. A., Cotran, R. S., Reiss, C. S., Burakoff, S. J., Fiers, W., and Ault, K. A.: Ia expression by vascular endothelium is inducible by activated T cells and by human γ interferon. J. Exp. Med. 157: 1339–1353, 1983
Pujol-Borrell, R., Hanafusua, T., Chiozato, L., and Bottazzo, G. S.: Lectin-induced expression of DR antigen on human cultured follicular thyroid cells. Nature 304: 71–73, 1983
Snyder, D. S., Beller, D. I., and Unanue, E. R.: Prostaglandins modulate macrophage Ia expression. Nature 299: 163–165, 1982
Steeg, P. S., Moore, R. N., Johnson, H. M., and Oppenheim, J. J.: Regulation of murine macrophage Ia antigen expression by a lymphokine with immune activity. J. Exp. Med. 156: 1780–1793, 1983
Steinmetz, M., Minard, K., Horvath, S., McNicholas, J., Frelinger, J., Wake, C., Long, E., Mach, B., and Hood, L.: A molecular map of the immune response region from the major histocompatibility complex of the mouse. Nature 300: 35–42, 1982
Thomas, P. S.: Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. U.S.A. 77: 5201–5205, 1980
Ullrich, A., Shine, J., Chirgwin, J., Pictet, R., Tischer, E., Rutter, W. J., and Goodman, H. M.: Rat insulin genes: Construction of plasmids containing the coding sequences. Science 196: 1313–1319, 1977
Wadgymar, A., Urmson, J., Baumal, R., and Halloran, P. F.: Changes in Ia expression in mouse kidney during acute graft-vs-host disease. J. Immunol. 132: 1826–1832, 1984
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Sinclair, G.D., Wadgymar, A., Halloran, P.F. et al. Graft-vs-host reactions induce H-2 class II gene transcription in host kidney cells. Immunogenetics 20, 503–511 (1984). https://doi.org/10.1007/BF00364353
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DOI: https://doi.org/10.1007/BF00364353