ROLE OF T-CELL SUBSETS IN IMMUNITY AGAINST INTRACELLULAR BACTERIA - EXPERIMENTAL INFECTIONS OF KNOCK-OUT MICE WITH LISTERIA-MONOCYTOGENES AND MYCOBACTERIUM-BOVIS BCG

The generation of knock-out mice with targeted gene deletions has alre ady proven its enormous value for our understanding of the antimicrobi al immune response. Here, we describe studies with knock-out mice defi cient in the TCR-beta gene, lacking alpha/beta T cells; in the TCR-del ta gene, lacking gamma/delta T cells; in the beta 2m gene, lacking bet a 2-microglobulin, and hence cell surface expressed MHC class I and fu nctional CD8 T cells; and in the H-2I-A beta gene, lacking cell surfac e expressed MHC class II and hence functional CD4 T cells. These mice were infected with Listeria monocytogenes or Mycobacterium bovis BCG a s representative microbes which primarily activate CDS T cells or CD4 T cells, respectively. Data described in this treatise demonstrate tha t the different gene deletions had an impact of varying degree on anti bacterial defense and on the formation of granulomatous lesions. At th e same time, the data point to a compensatory potential of the incompl ete immune system. We assume that deletions in the major immune effect or cells promote the emergence of a second line of defenders which fre quently remain silent in the normal immune system. Thus, our data illu strate as enormous redundancy of the immune system, which, however, is not abundant since it takes over essential functions in the immunodef icient situation.