CD57-LYMPHOCYTES ARE DERIVED FROM CD57- PRECURSORS BY DIFFERENTIATIONOCCURRING IN LATE IMMUNE-RESPONSES( T)

CD3(+) T cells expressing the 110-kDa CD57 antigen are found in surviv ors of renal, cardiac and bone marrow transplants, in patients with ac quired immune deficiency syndrome and in patients with rheumatoid arth ritis. They are also present in normal individuals and expand upon age ing. They do not grow in culture and their role in the immune response is poorly understood. The expression of the various isoforms of the l eukocyte common antigen (CD45) identifies a spectrum of differentiatio n ind CD4(+) and CD8(+) T cells ranging from naive (CD45RA(+)CD45RB(br ight)CD45RO(-)) through early primed cells (CD45RA(-)RB(bright)RO(dull )) to highly differentiated memory cells which are CD45RA(-)RB(dull)RO (bright). CD45 isoforms express by CD57(+) T cells showed distinct dif ferences between CD4(+) and CD8(+) populations, but in each case indic ated an advanced state of differentiation. The expression of T cell re ceptor V beta families was highly variable between individuals, but bo th CD57(+) and CD57(-) cells show a full range of the specificities te sted. V beta expression was more closely related within either the CD4 (+) or the CD8(+) subsets, irrespective of CD57 expression, than betwe en these subsets, suggesting a relationship between CD57(+) and CD57(- ) cells within the same T cell pool. This possibility was supported by experiments showing that CD3(+)CD57(+) lymphocytes were similar to CD 3(+)CD57(-) T cells in terms of the production of basic T cell cytokin es [interleukin (IL)-2, IL-4, and interferon-gamma]. Furthermore, in v itro stimulation of CD3(+)CD57- T cells in secondary mixed leukocyte r eaction or by co-culture with IL-2 and IL-4 induced the appearance of CD3(+)CD57(+) cells. These data strongly suggest that the expression o f CD57 is a differentiation event which occurs on CD57(-) T cells late in the immune response.