Decrease in CD8+ lymphocytes in atopic dermatitis is associated with a preferential loss of cytotoxic effector cells rather than suppressor inducer cells.
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Biomedical subjects
Publications and source records attributed to K Hanley-Yanez.
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In this report, we present data on heterogeneity of rat NK cells utilizing a combination of antibody and lectin-binding characteristics. Among NKR-P1bright NK cells, two discrete populations characterized as Lycopersicon esculentum lectin (L.E.)bright (60 to 80%) and L.E.dim (20 to 40%) were identified by flow cytometry. Comparison of the morphology of sorted NKR-P1bright/L.E.bright and NKR-P1bright/L.E.dim cells indicated that both were greater than 90% LGL. An analysis of the functional capabilities of the sub-populations indicated that NKR-P1bright/L.E.bright NK cells were more efficient in lysis of YAC-1 target cells (1743 LU20/10(7) cells) than were NKR-P1bright/L.E.dim cells (504 LU20/10(7) cells). Conversely, NKR-P1bright/L.E.dim NK cells were much more efficient at lysis of antibody-sensitized erythrocytes (antibody-dependent cellular cytotoxicity (ADCC)) (1412 LU20/10(7) cells) than were NKR-P1bright/L.E.bright cells (165 LU20/10(7) cells). Lysis of antibody sensitized P815 target cells yielded similar results as NKR-P1bright/L.E.dim cells and NKR-P1bright/L.E.bright cells had 905 LU20/10(7) and 189 LU20/10(7), respectively. Additional experiments indicated that NKR-P1bright/L.E.bright NK cells had the capacity to trigger lytic activity via NKR-P1 whereas NKR-P1bright/L.E.dim NK cells did not. NKR-P1bright/L.E.bright sorted cells had a greater capacity to form conjugates with YAC-1 target cells than did NKR-P1bright/L.E.dim sorted cells. Conversely, NKR-P1bright/L.E.dim NK cells were demonstrated to form E-A rosettes whereas the NKR-P1bright/L.E.bright NK cells were not. Additional experiments indicated that tomato lectin itself was not responsible for the differences in reverse ADCC activity or ADCC activity among the subsets. However, lysis of YAC-1 target cells was modulated to some degree by the lectin. These data indicate that NKR-P1bright/L.E.bright and NKR-P1bright/L.E.dim subpopulations of rat NK cells have different capacities for: 1) triggering through NKR-P1; and 2) E-A rosette formation and lysis of antibody-sensitized target cells by ADCC.
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The activation of large granular lymphocytes (LGLs)/natural killer (NK) cells with interleukin-2 (IL-2) has been shown to increase the ability of these cells to lyse NK-resistant tumor target cells. Activated LGLs, termed LAK (lymphokine-activated killer) cells, have been demonstrated to be of therapeutic value in vivo against metastatic tumors. The mechanism by which IL-2 induces broadened cytolytic capability, as well as the molecular basis of target recognition and killing by the activated cells has not yet been elucidated. Since carbohydrate moieties have been demonstrated to be of possible significance in the cytolytic cascade of a variety of effector cells, the current study was undertaken to determine if the activation of LGLs with IL-2 is accompanied by an alteration of cell-surface carbohydrates. Two-color flow cytometry was performed to identify LGL/NK cells in populations of nylon wool-nonadherent splenic mononuclear cells and to assess the binding of various lectins to activated as well as nonactivated LGLs. Increases were observed in the binding of four lectins to LGLs after IL-2 activation; Triticum vulgaris (wheat germ agglutinin), Phytolacca americana (pokeweed mitogen), Lycopersicon esculentum (tomato lectin), and Griffonia simplicifolia I-B4 (GSI-B4). The wheat germ, pokeweed, and tomato lectins recognize complex carbohydrates structure consisting of GlcNAc(Bl,4GlcNAc)n while GSI-B4 recognizes alpha-D-galactose terminal end groups. Lectin binding to the activated LGLs was homogenous (i.e., flow cytometry revealed only a single population of fluorescent cells). Lectin binding to LGLs prior to activation was more heterogeneous, however, the tomato lectin uniquely revealed a bimodal distribution of receptors. These data indicate that LGL/NK cells from the rat are heterogeneous in their ability to bind specific lectins, and that IL-2 activation of these cells results in altered expression of specific cell-surface carbohydrates.