Human CD8+ lymphocyte subpopulations were analyzed for their expression of CD8 alpha and CD8 beta subunits. Investigations with uncloned peripheral blood lymphocytes as well as cloned human natural killer and T cell subpopulations demonstrate that CD3- natural killer cells, T cell receptor gamma/delta, and CD4+CD8+ T cell clones express exclusively CD8 alpha gene products. Structural analysis of CD8 molecules demonstrates that CD8 alpha+/beta- T lymphocytes surface express 75-kDa CD8 alpha/alpha homodimers whereas CD8 alpha/beta lymphocytes express concomittantly two CD8 isoforms of different molecular masses (67 kDa and 75 kDa, respectively). Peptide mapping of these latter two isoforms suggests that CD8 is expressed as alpha/alpha homodimers and alpha/beta heterodimers on CD8 alpha/beta+ cells. Importantly, we found that the two CD8 isoforms behave functionally different. Thus, in contrast to CD8 alpha/beta+/CD8 alpha/alpha+ T lymphocytes, cytolytic activity of CD8 alpha/beta-/CD8 alpha/alpha+ T cell clones was not inhibited by anti-CD8 monoclonal antibodies and the latter were not induced to proliferate following CD3/CD8 cross-linking.

Immunological events are involved in the pathophysiology of chronic active hepatitis as indicated from the accumulation of T lymphocytes at the site of tissue damage. We generated T cell clones from liver biopsies of 3 patients with chronic active hepatitis B and 2 patients with primary biliary cirrhosis. These T cell clones (n = 84) were analyzed by means of T cell receptor (TcR) beta gene rearrangements to determine whether the infiltrate consists of a polyclonal or oligoclonal T cell population. The vast majority (62 of 64) of T cell clones from three different patients with chronic active hepatitis B showed no identical rearrangements of the TcR beta chain genes. In marked contrast, in both patients with primary biliary cirrhosis, T cell clones established were of limited diversity. Thus 5 out of 10 and 2 out of 10 T cell clones from one patient and 3 out of 9 and 2 out of 9 T cell clones from the second patient, respectively, showed identical TcR beta gene rearrangements. These data suggest that a clonal dominance is characteristic for local T cell responses in autoimmune liver disease such as primary biliary cirrhosis whereas in virus-induced chronic active hepatitis T cell activation occurs polyclonally.