Search tips
Search criteria 


Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1988 March 1; 167(3): 1124–1136.
PMCID: PMC2188904

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


The role of cytotoxic cells in in vivo immune functions such as allograft rejection is unknown. To begin to assess the function of cytolytic cells in vivo we have begun with cytolytic cell-specific functional molecules: we have isolated and characterized cytolytic cell- specific cDNA clones from cytolytic T cell clones, both encoding distinct serine esterases. The HF gene encodes a trypsin-like enzyme while the C11 gene encodes an enzyme with likely specificity for acidic residues. Here we demonstrate, using in situ hybridization with RNA probe, that both genes are expressed selectively in a subset of T lymphocytes that have infiltrated cardiac allografts. The phenotype of these cells is consistent with the most frequent phenotype of active CTL raised in vitro: they are predominantly CD4-, CD8+, MEL-14- T cell blasts. Thus the expression of these genes, each of which encodes serine esterase found in killer cell granules in vitro, is a valid marker for these cells in vivo as well. The kinetics of their accumulation is consistent with, but not proof of, a putative role in allograft rejection. It is likely that HF and C11 gene expression will be of diagnostic value.

Full Text

The Full Text of this article is available as a PDF (944K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ascher NL, Hoffman R, Chen S, Simmons RL. Specific and nonspecific infiltration of sponge matrix allografts by specifically sensitized cytotoxic lymphocytes. Cell Immunol. 1980 Jun;52(1):38–47. [PubMed]
  • Hanto DW, Hopt UT, Hoffman R, Simmons RL. Recruitment of unsensitized circulating lymphocytes to sites of allogeneic cellular interactions. Transplantation. 1982 May;33(5):541–546. [PubMed]
  • Steinmuller D. Which T cells mediate allograft rejection? Transplantation. 1985 Sep;40(3):229–233. [PubMed]
  • Cobbold S, Waldmann H. Skin allograft rejection by L3/T4+ and Lyt-2+ T cell subsets. Transplantation. 1986 May;41(5):634–639. [PubMed]
  • Golding H, Munitz TI, Singer A. Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity. J Exp Med. 1985 Sep 1;162(3):943–961. [PMC free article] [PubMed]
  • Swain SL, Panfili PR. Helper cells activated by allogeneic H-2K or H-2D differences have a Ly phenotype distinct from those responsive to I differences. J Immunol. 1979 Feb;122(2):383–391. [PubMed]
  • Podack ER, Dennert G. Assembly of two types of tubules with putative cytolytic function by cloned natural killer cells. Nature. 302(5907):442–445. [PubMed]
  • Dennert G, Podack ER. Cytolysis by H-2-specific T killer cells. Assembly of tubular complexes on target membranes. J Exp Med. 1983 May 1;157(5):1483–1495. [PMC free article] [PubMed]
  • Henkart PA, Millard PJ, Reynolds CW, Henkart MP. Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors. J Exp Med. 1984 Jul 1;160(1):75–93. [PMC free article] [PubMed]
  • MacDermott RP, Schmidt RE, Caulfield JP, Hein A, Bartley GT, Ritz J, Schlossman SF, Austen KF, Stevens RL. Proteoglycans in cell-mediated cytotoxicity. Identification, localization, and exocytosis of a chondroitin sulfate proteoglycan from human cloned natural killer cells during target cell lysis. J Exp Med. 1985 Dec 1;162(6):1771–1787. [PMC free article] [PubMed]
  • Petty HR, Hermann W, Dereski W, Frey T, McConnell HM. Activatable esterase activity of murine natural killer cell--YAC tumour cell conjugates. J Cell Sci. 1984 Dec;72:1–13. [PubMed]
  • Pasternack MS, Eisen HN. A novel serine esterase expressed by cytotoxic T lymphocytes. Nature. 314(6013):743–745. [PubMed]
  • Tschopp J, Müller-Eberhard HJ, Podack ER. Formation of transmembrane tubules by spontaneous polymerization of the hydrophilic complement protein C9. Nature. 1982 Aug 5;298(5874):534–538. [PubMed]
  • Young JD, Cohn ZA, Podack ER. The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities. Science. 1986 Jul 11;233(4760):184–190. [PubMed]
  • Young JD, Hengartner H, Podack ER, Cohn ZA. Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell. 1986 Mar 28;44(6):849–859. [PubMed]
  • Chang TW, Eisen HN. Effects of N alpha-tosyl-L-lysyl-chloromethylketone on the activity of cytotoxic T lymphocytes. J Immunol. 1980 Mar;124(3):1028–1033. [PubMed]
  • 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]
  • Gershenfeld HK, Weissman IL. Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte. Science. 1986 May 16;232(4752):854–858. [PubMed]
  • Lobe CG, Finlay BB, Paranchych W, Paetkau VH, Bleackley RC. Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes. Science. 1986 May 16;232(4752):858–861. [PubMed]
  • Brunet JF, Dosseto M, Denizot F, Mattei MG, Clark WR, Haqqi TM, Ferrier P, Nabholz M, Schmitt-Verhulst AM, Luciani MF, et al. 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. [PubMed]
  • Masson D, Tschopp J. A family of serine esterases in lytic granules of cytolytic T lymphocytes. Cell. 1987 Jun 5;49(5):679–685. [PubMed]
  • GOWANS JL, KNIGHT EJ. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. [PubMed]
  • Reichert RA, Gallatin WM, Weissman IL, Butcher EC. Germinal center B cells lack homing receptors necessary for normal lymphocyte recirculation. J Exp Med. 1983 Mar 1;157(3):813–827. [PMC free article] [PubMed]
  • Gallatin M, St John TP, Siegelman M, Reichert R, Butcher EC, Weissman IL. Lymphocyte homing receptors. Cell. 1986 Mar 14;44(5):673–680. [PubMed]
  • Billingham M, Warnke R, Weissman IL. The cellular infiltrate in cardiac allograft rejection in mice. Transplantation. 1977 Feb;23(2):171–176. [PubMed]
  • Parks DR, Herzenberg LA. Fluorescence-activated cell sorting: theory, experimental optimization, and applications in lymphoid cell biology. Methods Enzymol. 1984;108:197–241. [PubMed]
  • Berke G, Rosen D. Are lytic granules and perforin 1 involved in lysis induced by in vivo-primed peritoneal exudate cytolytic T lymphocytes? Transplant Proc. 1987 Feb;19(1 Pt 1):412–416. [PubMed]
  • Tilney NL, Strom TB, Macpherson SG, Carpenter CB. Surface properties and functional characteristics of infiltrating cells harvested from acutely rejecting cardiac allografts in inbred rats. Transplantation. 1975 Oct;20(4):323–330. [PubMed]
  • Brunet JF, Denizot F, Suzan M, Haas W, Mencia-Huerta JM, Berke G, Luciani MF, Golstein P. CTLA-1 and CTLA-3 serine esterase transcripts are detected mostly in cytotoxic T cells, but not only and not always. J Immunol. 1987 Jun 15;138(12):4102–4105. [PubMed]
  • 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. [PMC free article] [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press