EXPERIMENTAL YERSINIA-ENTEROCOLITICA INFECTION IN EUTHYMIC AND T-CELL-DEFICIENT ATHYMIC NUDE C57BL 6 MICE - COMPARISON OF TIME-COURSE, HISTOMORPHOLOGY, AND IMMUNE-RESPONSE/

To elucidate the role of T lymphocytes in primary infection with Yersi nia enterocolitica, we investigated the elimination rate of this patho gen, the histomorphology of tissue lesions, and the immune responses o f athymic T-cell-deficient C57BL/6 nude mice and their euthymic litter mates after parenteral infection with Y. enterocolitica of serotype 0: 8. While a low inoculum of 3 x 10(2) Y. enterocolitica cells (about 0. 01 times the median lethal dose for normal C57BL/6 mice) was cleared b y normal C57BL/6 mice within 7 to 10 days, athymic nude C57BL/6 mice d eveloped progressive infections after this inoculum, leading to death on days 20 to 25 postinfection (p.i.). While normal C57BL/6 mice exper ienced short-term transient infections, nude mice exhibited a biphasic , progressive infectious process. Thus, in the early phase (days 1 to 7 p.i.), a rapid influx of CD11b/18-positive cells (Mac-1 antigen) and natural killer cells was evident in the spleens and livers of the nud e mice. The late phase (from day 8 p.i. onward) was characterized by a rapid progression of the infection and a further influx of CD11b/18-p ositive cells into the liver accompanied by an increase in bacterial c ounts and development of tissue lesions particularly in the liver and spleen. In normal mice, granuloma-like lesions composed of CD11b/18-, CD4-, and CD8-positive cells could be observed. However, granulomata w ere not found in nude mice. Yersinia-specific immunoglobulin G antibod ies appeared on day 15 p.i. in the sera of normal mice, while nude mic e failed to develop significant antibody titers. Adoptive transfer of Yersinia-specific T cells into athymic nude mice mediated resistance t o Y. enterocolitica infection and restored both the ability of granulo ma formation and the production of specific antibodies. In summary, th e data presented herein strongly suggest that T lymphocytes play an es sential role in the defense of C57BL/6 mice against Y. enterocolitica.