VIRUS-INDUCED POLYCLONAL T-CELL ACTIVATION IS FOLLOWED BY APOPTOSIS -PARTITIONING OF CD8(-CELLS BASED ON ALPHA-4 INTEGRIN EXPRESSION() T)

Systemic infection with lymphocytic choriomeningitis virus (LCMV) is a ccompanied by marked splenomegaly, primarily reflecting the accumulati on of CD8(+) T cells with an activated phenotype (e.g. VLA-4(hi)). Ana lysis of DNA content using 7-aminoactinomycin-D revealed that as many as 30% of CD8(+) T cells are cycling around day 6 post-infection and t hat virtually all cycling cells express a high level of VLA-4. In acco rd with the relatively stable CD4(+) cell number, only few cycling CD4 (+) cells were observed, Following virus control, splenic lymphocyte n umbers decreased gradually and during this period many apoptotic cells were detected in the white pulp using terminal deoxynucleotidyl trans ferase-mediated dUTP-biotin nick end labeling. Flow cytometric analysi s of DNA content revealed a high frequency of cells with subnormal lev els of DNA in the CD8(+)VLA-4(hi) subset, whereas the frequency was lo w for other lymphocyte subsets studied (CD4(+), CD8(+)VLA-4(lo) and a cells), In addition, numbers of CD8(+)VLA-4(hi) cells constitute simil ar to 30% of splenocytes at the peak of the response and undergo prefe rential decrease during normalization of splenocyte numbers, Together these findings indicate that LCMV-induced activation of T cells is fol lowed by apoptosis of many of the activated cells, Those CD8(+)VLA-4(h i) cells which do persist in LCMV immune mice are more sensitive to tr eatment with the cell-cycle-specific drug hydroxyurea than are phenoty pically naive T cells, Our results therefore indicate that LCMV infect ion induces polyclonal activation of CD8(+) cells which is followed by apoptosis of most of the triggered cells while a smaller subset persi sts as a primed population which include cycling cells.