Activated CD8+ T cells are increased in bronchoalveolar lavage (BAL) fluids from systemic sclerosis (SSc) patients with alveolitis. Analysis of T cell antigen receptor (TCR) expression by BAL CD8+ T cells shows a consistent pattern of junctional region lengths in some TCR V gene families over time. Predominance of one or two TCR junctional lengths suggests an oligoclonal expansion of these T cells. We hypothesize that oligoclonal CD8+ T cells cause tissue damage in SSc through cytolytic and cytokine effects. To test this, we isolated and cloned Vβ3+CD8+ T cells from BAL fluid from patient 1, Vβ12+CD8+ T cells from patient 2, Vβ16+CD8+ T cells from patient 3, Vβ17+CD8+ T cells from patient 4, and Vβ20+CD8+ T cells from patient 5. Expression of CD8 and the desired TCRVβ on the T cell clones was confirmed by flow cytometry and DNA sequence analysis. Of 72 clones, 37 have been tested to date for functional activities. These T cell clones had cytolytic activity against autologous fibroblasts and Epstein-Barr virus-transformed B cells. The T cells used the perforin-mediated pathway for target cell lysis, which could be blocked by concanamycin A. CD28+CD8+ clones had higher cytolytic activity than CD28-CD8+ ones. Analysis of cytokine mRNAs expression showed that the majority (20/37) of CD8+ T cell clones from SSc patients had Tc2 phenotype, producing IL-4 and IL-10, but not IFNγ or IL-2. In contrast, only 3/12 CD8+ T cell clones from a control BAL fluid had Tc2 pattern of cytokine production. These data suggest that clonally expanded CD8+ T cells in the lungs of SSc patients may contribute to tissue damage through cytolytic activity and cytokine production.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology