A Serine Protease-Encoding Gene That Marks Activated Cytotoxic T Cells In Vivo and In Vitro
Activated cytotoxic T lymphocytes (CTLs) are presumed to be the effectors in the lysis of virally infected or transformed host cells, the mediators of graft rejection, and the potential culprits in a number of autoimmune diseases. Unfortunately, there is no marker available that specifically identifies these cells in vivo, making it difficult to prove unequivocally that CTLs are the effector cells in these immune functions. Mature T cells are usually divided into subsets on the basis of their surface phenotype: Those that express the CD8 antigen are assumed to be potential cytotoxic cells, and those that express the CD4 antigen, potential helper cells. However, the identification of CD4+CD8- CTLs (Golding et al. 1985) and CD4-CD8+ helper cells (Swain and Panfili 1979) both in vitro and in graft rejection in vivo (Rosenberg et al. 1987) limits the usefulness of this division. A more serious problem with using phenotype to imply function is that these markers are expressed on both active and resting T cells. Thus, they cannot be used to distinguish between the cells participating in a localized immune response and those nonspecifically present at the site. To identify cytotoxic lymphocytes more accurately, we used a molecular genetic approach to isolate genes expressed by these cells.
KeywordsSerine Protease Esterase Activity Experimental Allergic Encephalomyelitis Specificity Pocket Serine Esterase
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- Anderson WF, Matthews BW, Woodbury RG (1978) Crystallographic data for a group specific protease from rat intestine. Biochemistry 17:819Google Scholar
- Brunet JF, Dosseto M, Denizot F, Mattei MG, Clark WR, Haqqi TH, Ferrier P, Nabholz M, Schmitt-Verhulst AM, Luciani MF, Golstein P (1986) The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14. Nature 322:268–271PubMedCrossRefGoogle Scholar
- Dennert G, Anderson CG, Prochazka G (1987) High activity of N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester serine esterase and cytolytic perforin in cloned cell lines is not demonstrable in in-vivo-induced cytotoxic effector cells. Proc Natl Acad Sci USA 84:5004–5008PubMedCrossRefGoogle Scholar
- Mueller C, Gershenfeld HK, Lobe CG, Okada CY, Bleackley RC, Weissman IL (1988) 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 167:1124–1136PubMedCrossRefGoogle Scholar
- Murphy MEP, Bleackley RC, Gershenfeld HK, Weissman IL, James MNG (1988) Comparative molecular models for two serine proteinases from cytotoxic T lymphocytes, (manuscript in preparation)Google Scholar