The kinetics of lymphoid cell proliferation in the tuberculous mouse spleen

Abstract

Cell proliferation in the spleen and delayed hypersensitivity to tuberculin are maximum on Day 12 of a virulent tuberculous infection in mice. At this time, cytokinetic analysis of the small- to medium-sized lymphocytes arranged in clusters in the red pulp of the spleen yielded a mean generation time of 11 hr with evidence of at least four successive divisions. Some of the proliferating cells subsequently died in situ or migrated into the peripheral blood. The localization of labeled spleen cells after transfer from M. tuberculosis-or Listeria-sensitized mice was not related to the antigen concentration in the organs of tuberculous recipients. Compared with normal spleen cells, those from mice sensitized with either organism accumulated more rapidly in spleens of tuberculous recipients. Their initial intravascular localization in the liver was influenced by specific sensitization, but localization in granulomas was comparable for cells sensitive to either organism; and in each case was significantly greater than for cells from nonsensitive donors. Proliferating bone marrow cells from specifically sensitized mice aggregated in the livers of recipients in numbers two to three times greater than did sensitized spleen cells. Initially, most labeled bone marrow cells were located intravascularly in recipient livers. Within 24 hr, they had disappeared from this location, but labeled cells persisted within granulomas. Over 85% of the labeled cells in recipients of spleen cells were identified as lymphocytes, whereas 26–52% of those found in recipients of bone marrow cells were macrophages. Only the latter were retained at granulomas in conspicuous numbers.