Natural Killer Activity Of Spleen Cells Research Articles

Inhibition of effector cell functions in natural killer cell activity (NK) and antibody-dependent cellular cytotoxicity (ADCC) in mice by normal and cancer sera.

AbstractEffector cells mediating natural killer (NK) cell activity and antibody‐dependent cellular cytotoxicity (ADCC) have been receiving considerable interest recently as they may represent an additional cellular defense mechanism against maglinancy. Spleen cells from normal young C3H (MTV+) female mice were found to have relatively high natural killer (NK) activities toward RL 1 and YAC‐1 tumor cell lines and high antibody‐dependent cell‐mediated cytotoxicity (ADCC) activities toward chicken RBC and SB tumor targets. Serum inhibition of NK and ADCC activities was either not demonstrable or only seen at low levels in the young mice. Following injection of a transplantable mammary adenocarcinoma that grew progressively in these mice, both NK and ADCC activities decreased and serummediated inhibition of both NK and ADCC increased as the tumors grew. NK and ADCC activities declined with age in C3H (MTV+) mice, and the serum inhibition of NK and ADCC activities of young mice increased with age. Aging mice, however, which had developed spontaneous mammary adenocarcinoma, although having increased levels of inhibitor against both NK and ADCC activities and decreased NK and ADCC activities of their spleen cells as compared to young normal mice, did not have different levels from those of aging mice which had not developed the mammary tumor. Correlation was poor between the amount of serum inhibitor(s) on NK and ADCC activities. NK versus RL 1 and ADCC for chicken RBC were not correlated, but NK versus YAC‐1 and ADCC for the tumor cell line SB appeared to be correlated. Decreasing NK and ADCC and increasing serum inhibitory activity toward these functions appeared to correlate with tumor progression. Sera from transplantable tumor‐bearing young C3H mice contained increased amounts of circulating immune complexes, but the amount of circulating immune complexes was only weakly correlated with the serum inhibition of NK activity of spleen cells from young animals by sera from tumor‐bearing young mice. These findings indicate that a serum blocking factor(s) that can inhibit natural cell‐mediated cytotoxicity or antibody‐mediated cytotoxicity in vitro must be considered in analyzing host resistance to tumor growth.

Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice. I. Characterization of natural killer cell induction

Lymphocytic choriomeningitis virus (LCMV) infection of C3H/St, nude (BALB/c background), and other mice induced high levels of natural killer (NK) cell activity in the spleen and peritoneum. L-929 cells were used as targetsand were not lysed by spleen or peritoneal cells from uninfected mice. The cytotoxic cells were characterized as NK cells because they were nonadherent, nonphagocytic lymphocytes lacking theta and immunoglobulin antigens on their plasma membranes. Their activity was sensitive to 6 mM EDTA and to heating for 5 h at 37 degrees C, but resisted treatment with 0.5 percent trypsin. No role for antibody could be demonstrated in these assays. Relative to cytotoxic T-cell activity, the induction of NK cell activity was resistant to X-irradiation of mice with 1,000 rads but was sensitive if mice were first treated with Strontium-89, a bone-seeking isotope. NK cells were induced by LCMV in all tested strains of mice. In C3H/St mice NK cell activity was detected as early as 1 day and peaked at 3 days postinfection. Maximum activity in C3H/St mice was observed in mice 5-10 wk of age, but significant NK activity was also induced in newborns, which subsequently carried virus in their tissues for the duration of their lives. Older LCMV-carriers did not have detectable spleen NK cell activity. No memory oranamnestic response could be demonstrated for NK cell induction. NK cell activity was not induced by LCMV challenge of LCMV-immune mice, but was induced in those mice by infection with Pichinde virus, a closely related virus. The advent of NK cell activity correlated with the synthesis of interferon in LCMV-infected mice. Culture fluids lacking virus infectivity but containing interferon induced cytotoxic cell activity in nude and C3H/St mice. These experiments suggest that LCMV induced NK cells via an interferon-dependent mechanism. When studied in several strains of mice, the continued expression of NK cell activity did not seem to directly correlate with spleen interferon levels, suggesting that additional factors may play a role as well in maintaining the activity of the NK cell in vivo.

Identification of a cell-surface antigen selectively expressed on the natural killer cell.

We have studied the cell-surface phenotype of natural killer (NK) cells of NZB and B6 mice which react to an MuLV+ lymphoid tumor. (a) NK cells do not express Thy1, Ly2, or Ig surface markers. (b) NK cells express an antigen recognized by C3H anti-CE antiserum ('anti-Ly1.2 antiserum'). Inasmuch as NK activity of spleen cells from B6 and B6/Ly1.1 congenic strains were both equally sensitive to C3H anti-CE antiserum, the NK antigen is distinct from Ly1.2. This point was confirmed by the observation that alphaNK activity was removed by absorption of C3H anti-CE antiserum with spleen cells from either B6 or B6/Ly1.1 congenic strains. Absorption of C3H alphaCE serum with BALB/c thymocytes and spleen cells (which are Ly1.2+NK-) removed anti-Ly1.2 activity and left anti-NK activity intact. This absorption step could be circumvented by inserting the BALB/c genotype into the recipient immunized to CE cells (i.e., (C3H X BALB/c)F1 alphaCE spleen cells). This antiserum, provisionally termed 'anti-NK', defines a new subclass of lymphocytes which may play a central role in the immunosurveillance against tumors.