CYTOLYTIC ACTIVITY OF INTESTINAL INTRAEPITHELIAL LYMPHOCYTES IN GERM-FREE MICE IS STRAIN-DEPENDENT AND DETERMINED BY T-CELLS EXPRESSING GAMMA-DELTA-T-CELL ANTIGEN RECEPTORS

We have compared the cytolytic activities and the cellular compositions of the intestinal intraepithelial lymphocyte (i-IEL) populations in three different combinations of conventional (CV) and germ-free (GF) mice. Cytolytic activity of i-IELs expressing gammabeta T-cell antigen receptors (TCRs) is strain dependent in CV mice (high vs. low), and this strain-dependent variability is unaltered in the GF condition. Although absolute numbers of gammadelta i-IELs are slightly decreased, the composition of CD8alphaalpha+ and CD4-CD8- subsets and the usage of TCR gamma- and delta-chain variable gene segments by gammadelta i-IELs remain the same in GF mice. By contrast, cytolytic activity of alphabeta TCR-expressing i-IELs is uniformly high in CV mice but attenuated sharply in the GF condition. A conspicuous decrease in the total numbers of alphabeta i-IELs is also noted, and CD8alphabeta+ and CD4+CD8+ subsets are reduced, whereas the CD8alphaalpha+ subset is expanded in GF mice. These results indicate that microbial deprivation preferentially influences the alphabeta i-IEL population to decrease and become noncytolytic but has little effect on the pool size or characteristics of gammadelta i-IELs. Consequently, cytolytic activity of freshly isolated i-IELs from GF mice is determined by T cells expressing gammadelta TCRs and is found to be strain dependent.