Suppression by Alpha-Fetoprotein of Murine Natural Killer Cell Activity Stimulated in Vitro and in Vivo by Interferon and Interleukin 2 (original) (raw)
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Cellular Immunology, 1985
Cord blood lymphocytes (CBL) were compared with adult peripheral blood lymphocytes (a-PBL) for their: (i) natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities, (ii) target-binding capacity, (iii) ability to induce soluble natural killer cytotoxic factor (NKCF), (iv) interferon (IFN>, interleukin 2 (IL-2)-, and lectin-induced augmentation of NK activity, and (v) ability to produce IFN against tumor targets in vitro. CBL depleted of adherent cells and Percoll-separated, NK-enriched subpopulations demonstrated significantly lower NK, ADCC, and target-binding activities compared to a-PBL. CBL produced significantly lower levels of NKCF directed against K562 tumor targets in comparison with a-PBL. Although the NK activity of CBL was not stimulated by either IFN or IL2 to the same levels shown by a-PBL, the percentage enhancement of cytotoxicity of CBL by IFN and IL-2 was greater than that of a-PBL. Lectin-induced enhancement of cytotoxicity was significantly greater for CBL in comparison with a-PBL. Further, the ability of CBL lymphocytes to produce EN-r in vitro against K562 target cells was significantly lower than that of adult PBL. These studies suggest an association between decreased NK, ADCC, and target-binding activities, induction of NKCF and IFN production by CBL, and increased susceptibility of neonates to infection. o 1985 Academic F'ress, Inc.
Scandinavian Journal of Immunology, 1984
We have studied the effeci of interfcron in \ivo (induced by polyinnsinic-polycytidylic acid (pIC)l on the niitur^il killer INK) cell lytic activity and on ihc numhcrs of t^irge (iranular lymphocytes (l.Cil.l and liirget-binding cells (TBC) in diffcreni lymphoid cumpariments.. One day after the pK' induction tbe spleeti eonlamed two-lo lour-lold increased lytic activity without a Mgnifieanl change in percentages ()f VW and l.GL. In ihe peripheral blood tbe lytic iiciivity was 12-in 4(l-f()ld higher, and a concomilanl clear increase in the number of LCiL and VBC was seen. In the lungs ihe increase in lylic activity wiis K-lo Kvlnld and in tbe numher of l.GLs ca. 3-fold. These results demonstrate ihat not only ihe lylic acliviiy of the pre-existing NK cells hut also the tolal amount of NK cells is clearly elevated in the body, but this eould he seen more significantly in oiher highly NK-active organs than the spleen.
Modulation of human nk cells by interferon and prostaglandin E2
Molecular Immunology, 1982
Our studies have shown that stimulation of human natural killer (NK) cells by poly I:C does not depend on or require monocytes. In contrast. the presence of monocytes in a mixed population of mononuclear cells stimulated by poly I:C suppresses NK activity. The suppression can be partially overcome if indomethacin (10m6 M) is added to the culture during stimulation. Culture supernatants from poly I:C stimulated monocytes do not have detectable levels of anti-viral activity but contained appreciable amounts of PGE2. Our results offer an explanation as to how NK cells may protect themselves from suppression by PGE*. We have demonstrated that IFN-activated NK cells become resistant to PGE*-mediated suppression; moreover the suppression does not require cells other than the large granular lymphocytes, the major effector cell type for NK. Taken together, the data suggest that stimulation of NK cells is dependent on and regulated by the relative levels of interferon produced by lymphocytes and PGE, produced by monocytes.
Journal of Experimental Medicine, 1989
Human B lymphoblastoid cell lines facilitate the growth in vitro of human NK cells and of T cell clones (1-4), and together with a source of IL-2, have been successfully used to maintain both NK and T cell clones in culture (1, 2). We have shown that irradiated B lymphoblastoid cell lines induce proliferation of purified human NK cells only in synergy with IL-2 (3). They also facilitate continued proliferation and enhance the cloning efficiency of purified human NK cells in limiting dilution assays in the presence of IL-2 without increasing the proportion (>507o) of NK cells entering the cell cycle in response to IL-2 (4). During culture of total PBMC with irradiated B cell lines, NK cells become activated, as shown by increased cytotoxic activity, by proliferation, and by expression of surface activation antigens such as class II HLA antigens, transferrin receptors, and IL-2 receptors (5, 6). In these cultures, a preferential proliferation of CD16+ CD56(NKH-1)+ CD3 -NK cells is observed (6) : in 10-d cultures, NK cell number is increased 25-fold, whereas T cell number is increased only 3-fold . Elimination of CD4 + cells or the presence of an anti-IL-2 antiserum completely prevents NK cell proliferation (6), suggesting that this probably depends on the production of IL-2 by CD4 + T cells upon allogeneic stimulation . However, the B cell lines also contribute directly to the proliferation of NK cells because in the absence of B cell lines neither high doses of IL-2 alone nor stimulation by allogeneic PBMC induce preferential proliferation of NK cells (6) .
British Journal of Cancer, 1984
The in vivo and in vitro effects of human a-interferon (IFN) on blood natural killer (NK) cell activity were studied in patients with malignant melanoma. The initial response to an i.m. injection of IFN was a depression of blood NK cell activity, being detectable at 4h and reaching a nadir at 12h. Blood NK cell activity returned to or exceeded pretreatment levels within 24 h. The frequency of large granular lymphocytes among peripheral blood lymphocytes (PBL), however, remained unchanged during the first 24h of IFN treatment. In a single cell cytotoxicity assay in agarose the number of lymphocytes forming conjugates with K562 target cells was not affected at 12-h points of IFN treatment, while the frequency of lytic conjugates with dead target cells was decreased by 12 h. Thus, the number of active NK cells was reduced by IFN administration. While in vitro exposure to IFN resulted in an augmentation of NK cell activity of PBL from untreated patients, IFN failed to enhance the activity of PBL obtained 12h post IFN injection. When PBL obtained 12h after IFN injection were cultured overnight, they recovered their responsiveness to NKboosting effects of IFN. Blood monocytes obtained at 12-h points from IFN-treated patients suppressed IFNinduced enhancement of NK cell activity, although these monocytes did not inhibit the base line level of NK cell activity. In contrast, the streptococcal preparation OK432 was able to augment NK cell activity of PBL obtained 12h post IFN administration and of control PBL even in the presence of suppressor monocytes. PBL obtained 24h post IFN injection expressing enhanced NK cell activity were also unresponsive to IFN in vitro. However, monocytes obtained 24h after IFN injection were no longer able to inhibit IFN-induced augmentation of NK cell activity. These results indicate that in vivo administration of IFN-a to cancer patients results in rapid and transient generation of suppressor monocytes capable of inhibiting IFNdependent development of functional NK cell activity, which could be responsible for the initial and transient decline in blood NK cell activity.
Comparison of NK Activity in Mouse Spleen and Peripheral Blood Lymphocytes
Immunobiology, 1988
Natural killer (NK) cells originating in mouse peripheral blood were studied with regard to their lytic activity against YAC-1 target cells and to their expression of asialo-GM1 marker on their surface. In Balb/c, CBA/LAK and A/J mice, PBL were found to be approximately twice as effective as splenocytes. Splenic and peripheral NK cells were shown by flow cytometry to have similar lytic potential per cell; the difference in NK activity found in the spleen and in PBL was solely due to the differences in the size of the NK cell population found in the two sites. Strain distribution of NK activity in PBL followed the same pattern observed in splenocytes. The difference in NK activity between CBA and Balb/c mice was shown to be due to the fact that the lytic potential per NK cell was approximately twice as high in the former.
Clinical Immunology and Immunopathology, 1985
Interleukin 2 (IL-2) can induce or enhance the cytotoxic activity of natural killer (NK) cells and lymphokine-activated killer (LAK) cells. The effects of fetal bovine serum (FBS) and human AB serum (HABS) on the IL-2-induced NK cell and LAK cell activities of large granular lymphoctyes (LGL) were measured, respectively, against the NKsensitive cell line KS62 and the LAK-sensitive cell line Daudi. FBS and HABS were essentially equivalent in their effects on IL-2-dependent NK activity with prolonged culture. However, with prolonged incubation from 1 to 5 days of PBMC in the presence of IL-2, there was considerably less generation of LAK cell activity in FBS (Day 3: 5.3 f 3.4 LU/lO' cells) compared to HABS (Day 3: 44.6 f 4.2 LU/lO' cells) (P < 0.05). These differences in IL-2-dependent LAK cell generation did not appear to be due to the lot of the FBS or to activating factors present in individual samples of HABS. Similarly, the suppressive effects of FBS could not be reversed with increasing concentrations of IL-2 ranging from 10 to 100 U/ml. Importantly, the presence of FBS in the cultures resulted in more cell death (15.9 ? 5.6%) at 4 days of culture compared to HABS (1.8 f 1 .O%) (P < 0.05). These results suggest that FBS may inhibit generation of LAK effector cells, but not NK cells in cultures containing IL-2 and that the use of HABS as a culture supplement is preferable to FBS in studies of human LAK cell function.
Regulation of natural killer cell activity by anti-I-region monoclonal antibodies*1
Cellular Immunology, 1984
The effects of a monoclonal antibody directed against immune response gene products on mouse NK activity were examined. In vivo administration of an anti-I-Ak antibody to C3H/He (H-2') mice modulated their peritoneal cell (PC) and spleen cell (SC) natural killer (NK) activity against YAC-1 lymphoma target cells in vitro. No such effect was observed when BALB/c (H-2d) mice were treated with this antibody. Administration of anti-I-A' antibody to mice before and after infection with Toxoplasma or treatment with poly(I:C) leads to suppression of NK activity in comparison to NK activity of mice infected with Toxoplasma or injected with poly(I:C) alone. A similar treatment regimen with M5/114 antibody which reacts with I-Ab, I-Ad, I-Ed, and I-Ek molecules resulted in decreased NK activity in BlO.D2 (H-2d) but not in BlO.BR (H-2') mice. Serum and cell culture supematant interferon (IFN) concentrations were not altered as a result of anti-I-A' treatment. Removal of adherent cells did not restore NK activity of anti-I-Ak-treated Toxoplasma-infected mice to levels obtained with mice infected with Toxoplasma. In contrast, depletion of Ly 2.1+ cells from nylon-wool nonadherent SC of mice treated with anti-I-Ak antibody, before and alter infection with Toxoplasma, resulted in restoration of NK activity to the same level as that observed in Toxoplasma-infected mice.