Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Nov;133(2):218–225.

In situ localization of HuHF serine protease mRNA and cytotoxic cell-associated antigens in human dermatoses. A novel method for the detection of cytotoxic cells in human tissues.

G S Wood 1, C Mueller 1, R A Warnke 1, I L Weissman 1
PMCID: PMC1880792  PMID: 2461088

Abstract

Human Hanukah Factor (HuHF) is a trypsinlike serine protease associated with cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Employing a radiolabeled RNA probe for the HuHF gene, cells containing HuHF mRNA in situ were detected in skin lesions from patients with a variety of reactive and neoplastic dermatoses including positive allergic contact dermatitis patch tests, lichen planus, erythrodermic psoriasis, Sezary syndrome, and poikilodermatous mycosis fungoides. The results were correlated with in situ studies of CTL/NK subsets as defined immunohistologically by a panel of monoclonal antibodies applied to sermiserial sections of the same tissue blocks used for the HuHF hybridizations. The results suggest that cytotoxic cells are present in each of these dermatoses, that they may be situated within either the epidermis or the dermis, and that they belong predominantly to the CTL subset because Leu-7+ or CD16+ cells (NK cells) were typically rare or absent. A variable proportion of cells expressed Leu-19 antigen (a marker for non-MHC-restricted cytotoxic cells); however, its rarity in several cases suggests that most of the HuHF+ cells identified in them belonged to the MHC-restricted, Leu-19- CTL subset. It is concluded that the correlation of molecular biologic and immunohistologic data will be a useful method for the further characterization of cytotoxic cell subsets in human dermatoses.

Full text

PDF
218

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brunet J. F., Dosseto M., Denizot F., Mattei M. G., Clark W. R., Haqqi T. M., Ferrier P., Nabholz M., Schmitt-Verhulst A. M., Luciani M. F. The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14. Nature. 1986 Jul 17;322(6076):268–271. doi: 10.1038/322268a0. [DOI] [PubMed] [Google Scholar]
  2. Chang T. W., Eisen H. N. Effects of N alpha-tosyl-L-lysyl-chloromethylketone on the activity of cytotoxic T lymphocytes. J Immunol. 1980 Mar;124(3):1028–1033. [PubMed] [Google Scholar]
  3. Garcia C. F., Weiss L. M., Warnke R. A., Wood G. S. Cutaneous follicular lymphoma. Am J Surg Pathol. 1986 Jul;10(7):454–463. doi: 10.1097/00000478-198607000-00002. [DOI] [PubMed] [Google Scholar]
  4. Gershenfeld H. K., Hershberger R. J., Mueller C., Weissman I. L. A T cell- and natural killer cell-specific, trypsin-like serine protease. Implications of a cytolytic cascade. Ann N Y Acad Sci. 1988;532:367–379. doi: 10.1111/j.1749-6632.1988.tb36354.x. [DOI] [PubMed] [Google Scholar]
  5. Gershenfeld H. K., Hershberger R. J., Shows T. B., Weissman I. L. Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1184–1188. doi: 10.1073/pnas.85.4.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gershenfeld H. K., Weissman I. L. Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte. Science. 1986 May 16;232(4752):854–858. doi: 10.1126/science.2422755. [DOI] [PubMed] [Google Scholar]
  7. Lanier L. L., Le A. M., Cwirla S., Federspiel N., Phillips J. H. Antigenic, functional, and molecular genetic studies of human natural killer cells and cytotoxic T lymphocytes not restricted by the major histocompatibility complex. Fed Proc. 1986 Nov;45(12):2823–2828. [PubMed] [Google Scholar]
  8. Lobe C. G., Finlay B. B., Paranchych W., Paetkau V. H., Bleackley R. C. Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes. Science. 1986 May 16;232(4752):858–861. doi: 10.1126/science.3518058. [DOI] [PubMed] [Google Scholar]
  9. Masson D., Tschopp J. A family of serine esterases in lytic granules of cytolytic T lymphocytes. Cell. 1987 Jun 5;49(5):679–685. doi: 10.1016/0092-8674(87)90544-7. [DOI] [PubMed] [Google Scholar]
  10. Masson D., Zamai M., Tschopp J. Identification of granzyme A isolated from cytotoxic T-lymphocyte-granules as one of the proteases encoded by CTL-specific genes. FEBS Lett. 1986 Nov 10;208(1):84–88. doi: 10.1016/0014-5793(86)81537-x. [DOI] [PubMed] [Google Scholar]
  11. Mueller C., Gershenfeld H. K., Lobe C. G., Okada C. Y., Bleackley R. C., Weissman I. L. A high proportion of T lymphocytes that infiltrate H-2-incompatible heart allografts in vivo express genes encoding cytotoxic cell-specific serine proteases, but do not express the MEL-14-defined lymph node homing receptor. J Exp Med. 1988 Mar 1;167(3):1124–1136. doi: 10.1084/jem.167.3.1124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Orosz C. G., Zinn N. E., Sirinek L., Ferguson R. M. In vivo mechanisms of alloreactivity. I. Frequency of donor-reactive cytotoxic T lymphocytes in sponge matrix allografts. Transplantation. 1986 Jan;41(1):75–83. [PubMed] [Google Scholar]
  13. Pasternack M. S., Verret C. R., Liu M. A., Eisen H. N. Serine esterase in cytolytic T lymphocytes. Nature. 1986 Aug 21;322(6081):740–743. doi: 10.1038/322740a0. [DOI] [PubMed] [Google Scholar]
  14. Ralfkiaer E., Wantzin G. L., Mason D. Y., Hou-Jensen K., Stein H., Thomsen K. Phenotypic characterization of lymphocyte subsets in mycosis fungoides. Comparison with large plaque parapsoriasis and benign chronic dermatoses. Am J Clin Pathol. 1985 Nov;84(5):610–619. doi: 10.1093/ajcp/84.5.610. [DOI] [PubMed] [Google Scholar]
  15. Redelman D., Hudig D. The mechanism of cell-mediated cytotoxicity. I. Killing by murine cytotoxic T lymphocytes requires cell surface thiols and activated proteases. J Immunol. 1980 Feb;124(2):870–878. [PubMed] [Google Scholar]
  16. Schmid J., Weissmann C. Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. J Immunol. 1987 Jul 1;139(1):250–256. [PubMed] [Google Scholar]
  17. Sedgwick J., Brostoff S., Mason D. Experimental allergic encephalomyelitis in the absence of a classical delayed-type hypersensitivity reaction. Severe paralytic disease correlates with the presence of interleukin 2 receptor-positive cells infiltrating the central nervous system. J Exp Med. 1987 Apr 1;165(4):1058–1075. doi: 10.1084/jem.165.4.1058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Strom T. B., Tilney N. L., Paradysz J. M., Bancewicz J., Carpenter C. B. Cellular components of allograft rejection: identity, specificity, and cytotoxic function of cells infiltrating acutely rejecting allografts. J Immunol. 1977 Jun;118(6):2020–2026. [PubMed] [Google Scholar]
  19. Wood G. S., Burke J. S., Horning S., Doggett R. S., Levy R., Warnke R. A. The immunologic and clinicopathologic heterogeneity of cutaneous lymphomas other than mycosis fungoides. Blood. 1983 Aug;62(2):464–472. [PubMed] [Google Scholar]
  20. Wood G. S., Warnke R. A. The immunologic phenotyping of bone marrow biopsies and aspirates: frozen section techniques. Blood. 1982 May;59(5):913–922. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES