| Summary |
Natural killer (NK) cells are naturally occurring and are a first line defense mechanism against viral infections and oncogenesis. They mediate lytic activity to tumor and virally transformed target cells. Human and non-human primate NK cells mediate lysis of various tumor cells including T cell lymphomas and the myeloid leukemia, K562. However, resting human NK cells do not mediate activity to B cell lymphomas. This study describes a previously unreported lymphocyte population in the rhesus monkey mediating strong NK activity to the human B cell lymphoma derived cell line, Raji, and characterizes the functional, morphological, and phentotypic characteristics of this effector cell population. Natural killer cell lytic activity of unstimulated cells from rhesus monkeys were detected against Raji, Daudi, RPMI-1738, and Molt human cell lines, the first three of which were EBV positive. The strong lytic activity to Raji was significantly higher than to any other cell line tested. Potential explanations for the activity of Raji are discussed as are the possible relevance to low incidence of EBV related diseases in rhesus monkeys. Analysis of in vitro functional parameters revealed that NK cells lytic to Raji are sensitive to pH and temperature changes and are slightly affected by decreasing serum concentrations. Lysis of Raji and K562 occurs very rapidly; significant lysis is observed after five minutes of incubation although maximum lysis requires four hours. Morphological characteristics were found to include Sephadex nonadherence and enrichment in the low density, LGL enriched fraction of Percoll. Prostaglandins are recognized as downregulators of intact and nonadherent human and murine NK cells. Addition of PGE₂ to intact rhesus NK cells significantly decreased activity to Raji and K562, although Sephadex passed cells were insensitive to the inhibitory effects of PGE₂. Cold target inhibition studies in which K562 partially blocked the activity to Raji targets suggested the existence of at least two populations of rhesus monkey NK cells. One population may recognize only Raji and a second may recognize both K562 and Raji. Studies of the phenotypic characteristics revealed enhanced lytic activity in the ERFC⁺ subpopulation. Analysis by MAbs revealed that essentially all of the activity to Raji was contained in the CD16 (Leu 11b) subpopulation while only a portion of the cells expressed CD2 (9.6) and CDS (0KT8) receptors. Depletion of CD4 (0KT4), HLA-DR (0KIa) or MAC-1 positive cells variably increased activity to Raji. Alloantigen specific CTL generated in vivo were depleted of Fc positive cells and assayed for lytic activity to their specific target and to Raji and K562 . These experiments revealed a functional separation of CTL and NK activity indicating that the cell population mediating lysis of Raji is not a CTL. These findings suggest that the effector population mediating NK activity to Raji and K562 have similar phenotypic characteristics. However, they appear to differ in their functional characteristics and in their regulation by PGE₂. |
