Natural killer cells in guinea pig spleen bear Fc receptors

The phenomenon of natural cytotoxicity or spontaneous cell-mediated cytotoxicity (SCMC) was investigated in guinea pigs and compared with two other in vitro cytotoxicity reactions: mitogen-induced cellular cytotoxicity (MICC) and antibody-dependent cellular cytotoxicity (ADCC). The same xenogeneic target cells were employed in all three cytotoxicity assays. Organ distribution studies revealed that SCMC effector cell activity was present in spleen and peripheral blood but not in thymocytes. Bone marrow cells possessed low levels of SCMC effector cell activity. The organ distribution of effector cell activities for MICC and ADCC paralleled that for SCMC. Studies of the cell surface characteristics of the SCMC effector cell revealed that spleen cells nonadherent to antigen-antibody but not to antigen-F(ab')₂ antibody-coated surfaces possessed markedly reduced SCMC effector cell activity. In addition, spleen cells depleted of Fc receptor-bearing cells by EA rosetting also possessed diminished SCMC effector cell activity, while cell populations enriched in Fc receptorbearing cells by EA resetting possessed enhanced SCMC effector cell activity. These fractionation techniques had similar effects on MICC and ADCC effector cell activity. Depletion of adherent spleen cells including macrophages by nylon wool column passage resulted in a population of cells with enhanced SCMC, MICC, and ADCC effector cell activity. Thus, in guinea pig spleen the effector cells mediating SCMC were shown to belong to a population of nonadherent Fc receptor-bearing lymphocytes possessing several cytotoxic capabilities including the potential of mediating MICC and ADCC.     

Sensitization of rat T cells to syngeneic tumor cultures by cocultivation in diffusion chambers.

Total population and T cell enriched fractions of rat spleen were cultivated in diffusion chambers implanted intraperitoneally to mice and rats. 10-16% of the input cells were recovered after 5 days. When the chambers were carried in the xenogeneic environment activation occurred as indicated by blastogenesis and non-discriminative cytotoxicity. Specific activation of the T population was induced by mixed lymphocyte-tumor culture in chambers implanted in rats. The presence of tumor cells induced blastogenesis, elevation of the proportion of Fc receptor positive cells and generated cytotoxic cells to the sensitizer tumor. The precursor of cytotoxic cells did not have Fc or C3 receptors since nylon wool colum passed fractions depleted from these cells by elimination of EA- or EAC-rosettes were also activated.     

Liver-associated macrophage precursors as natural cytotoxic effectors against Candida albicans and Yac-1 cells

Liver nonparenchymal cells of maleic anhydride divinyl ether or cyclophosphamide-treated mice were assayed for cytotoxic activity against the yeast form of Candida albicans. A strong increase in this activity was observed after both in vivo treatments, as compared to untreated control mice. The effector cell was enriched by nylon wool passage and separation of nonadherent liver nonparenchymal cells on a discontinuous Percoll gradient. By means of direct and indirect rosetting techniques, based on the presence of Fc receptors and the F4/80 and M143 macrophage surface markers, we could separate a nearly homogeneous effector cell population. It displayed, besides the candidacidal activity, Fc receptors and the M143 and F4/80 antigens, also strong natural cytotoxicity against Yac-1 lymphoma cells. When cultured in medium containing colony-stimulating factor-1, this effector population reacted with a strong proliferative response as measured through incorporation of tritiated thymidine. The data presented show that nonadherent, nonphagocytic macrophage precursors, which we characterized previously from in vitro bone marrow cultures, occur in vivo as organ-associated effector cells in the liver after elicitation with maleic anhydride divinyl ether or cyclophosphamide. These macrophage precursors have prior to their maturation the ability to serve as a microbicidal and tumoricidal natural killer cell.     

Human peripheral null lymphocytes. II. Producers of type-1 interferon upon stimulation with tumor cells, Herpes simplex virus and Corynebacterium parvum

Human blood lymphocytes, exposed for 6 to 24 h in vitro to tumor cells (K 562, IGR3, L1210), Herpes simplex virus type 1 (HSV) or Corynebacterium parvum (CP), produced high levels of anti-viral activity which was identified as type-1 interferon (IF). In mixed lymphocyte tumor cell cultures (MLTC), the generated type-1 IF was definitely shown to originate from the lymphocytes and not from the tumor cells. Supplementation of leukocyte cultures with 10% fetal calf serum instead 10% human AB serum had little influence on tumor cell-induced IF production, but strongly reduced CP-induced IF production. Lymphocyte fractionation procedures involving iron/plastic treatment, nylon wool columns, Ig-anti-Ig columns and rosette (E, EA) separation led to the identification of null cells as highly efficient producers of type-1 IF. T cells obtained by different ways (E-rosette sedimentation, passage through 1 nylon and 2 Ig-anti-Ig columns, or thoracic duct lymphocytes) were poor IF producers in response to tumor cells, HSV and CP, but secreted anti-viral activity when stimulated with phytohemagglutinin. In MLTC, the level of generated type-1 IF roughly stimulated with phytohemagglutinin. In MLTC, the level of generated type-1 IF roughly paralleled nautral killer (NK) cell activity. Evidence is presented that type-1 IF can be produced by an Fc receptor-negative null cell subset, whereas NK activity requires Fc receptor-positive cells. It is suggested that production of type-1 IF represents one of the earliest functions in the differentiation process of mononuclear phagocytes and is likely to develop before the appearance of Fc receptors, diffuse esterase staining and latex phagocytosis.     

Target-Effector Interaction in the Natural Killer Cell System

These results show that two subpopulations of target-binding cells (TBC) can be detected in the lymphoid organs of normal, nonimmunized mice. One cell type is not adherent to nylon wool columns and binds selectively to a large number of tumour cell targets which are susceptible to lysis by the natural killer (NK) cell. The rise and fall in the frequency of these nylon nonadherent TBC, with age, closely parallels the NK cell activity in these mice. Nylon nonadherent TBC were specific since they could be inhibited by subcellular sonicates of sensitive targets but not insensitive targets. The presence of these TBC in nude mice and their ability to pass through nylon wool columns is compatible with the suggestion that, like the NK cell, they may not be mature T cells, macrophages or B cells and hence represent a distinct but not yet defined subpopulation of lymphocytes. The genes controlling the frequency of TBC are inherited in a dominant fashion and are linked to the H-2 region. The strong correlation between the frequency of TBC in a population and the level of lysis provides strong indirect evidence that the TBC may represent, or be closely related to, the NK cell. In contrast, the second cell type(s), a nylon-adherent population, was not subject to any detectable genetic control and bound to targets nonspecifically. Furthermore, these nylon-adherent TBC differed from nylon-nonadherent TBC in their lack of correlation with lysis, age variations and organ distribution. We believe these observations provide the basis for the eventual understanding of the target structures and receptors involved in the NK cell system.     

Comparison of highly NK active human lymphocyte subsets separated by various procedures involving E, EA rosetting, density gradients and adherence to immune complexes

Lymphocyte subsets from human blood obtained by different procedures were analyzed for cytotoxic potential and phenotypic characteristics. Nylon wool column passed lymphocytes were fractionated on the basis of: (1) E and Fc gamma receptor expression, (2) cell density and Fc gamma receptor expression, (3) Fc gamma receptor expression. The cytotoxic subsets obtained by separation on the basis of E and EA rosetting differed in their phenotypic composition from those separated on the basis of density or on immune complex monolayers. The E- Fc gamma- population contained few LGL and OKM1 positive cells. The E- Fc gamma+ population was made up almost entirely of LGL and OKM1 positive cells. The low density population was highly enriched in LGLs; among these the Fc gamma- cells were OKT3 positive. In contrast to the E- population the low dense Fc gamma+ cells were mainly LGLs and were OKM1 positive. Fc gamma+ subsets had less killer activity against Daudi cells. The choice of procedure for obtaining a strongly cytotoxic population depends on the needs of particular experiments. Separation on the basis of E rosetting gave lower cell (62%) and cytotoxic (43%) recovery and required about twice the amount of blood and twice the time, as compared with the other 2 procedures. The cell fractions obtained this way allowed characterization of several phenotypically different active populations and showed a difference in cytotoxic potential against K562 and Daudi cells. Density fractionation isolated a highly cytotoxic subset with LGL morphology but this population was still heterogeneous phenotypically. With regard to enrichment of NK activity, the immune complex monolayer attachment method was the most efficient for total cell recovery and for the time taken to perform it.     

Concanavalin-A-induced Suppressor Lymphocytes in Normal Individuals

Adherence of human lymphocytes to allogeneic tumour cell monolayers was found to depend on the presence of monocytes. Adherent lymphocytes could be separated from tumour cells by treatment with lidocaine followed by nylon wool passage. Tumour-adherent cells (70% E-RFC, 45% Fc gamma-R, 23% Fc mu-R, 5% monocytes) exhibited enriched natural killer (NK) activity not only against the tumour cell line used for isolation but also against seven other targets. When T cells were isolated subsequently as E-rosettes by density gradient centrifugation through Percoll, the enrichment in cytotoxicity was even more pronounced. Tumour-adherent T cells were severalfold enriched in both NK and antibody-dependent cell-mediated cytotoxicity (ADCC) activity. However, this enrichment was not paralleled by a concomitant increase in the number of T gamma cells (tumour-adherent T cells: 17% T gamma, 40% T mu ; tumour-nonadherent T cells: 12% T gamma, 60% T mu). Marked differences could be observed by staining with a monoclonal antibody that was raised against human leukaemic T gamma cells of high NK and ADCC activity. This antibody (T 8-11) stained 60% of tumour-adherent T cells, 20% of nonadherent T cells and 29% of T-cell controls. These results indicate that the spontaneous cytotoxic activity of human T cells resides within a small population, most of which are characterized by a specific surface antigen but not by conventional Fc gamma receptors.     

Control of primary IgM antibody responses to H-2 alloantigens by antigen-bearing live B lymphocytes

Alloantigen-bearing (H-2d+) peripheral red blood cells, but not red cell-depleted H-2d+ spleen cells, induce primary IgM anti-H-2d plaque-forming cell responses. In this study it is reported that the primary antibody responses to H-2d+ peripheral red blood cells can be markedly suppressed by a subpopulation of H-2d+ spleen cells when they are injected simultaneously or a few days before injection of red blood cells. This suppression was antigen (H-2d)-specific, did not depend on T cells of either the donor or the recipient, and strictly required live donor cells. An energy-dependent action of the donor cell cortex and some proliferation of donor cells in the recipient seemed to be involved in the mechanism of suppression. The donor-suppressor cell type was largely present in the spleen but not in the bone marrow and thymus, and was present in the spleen of athymic nude mice. The suppressor cells displayed the properties of B lymphocytes: they adhered to the nylon wool but not to glass, were of relatively low density (rho less than 1.09), and were surface Ig+, Ia+, Fc receptor-positive but Thy-1-. H-2d+ suppressor-donor B lymphocytes might directly signal to antigen-specific recipient B cells competing with the signal provided by H-2d+ red blood cells for the B cell activation.     

Sequential Changes in T and B Lymphocyte Responses to Herpes Simplex Virus in Man

Lymphocytes of seven patients with primary herpetic infection, twenty-three patients with recurrent herpes labialis and of nineteen control subjects were separated into T and B enriched cells by the use of nylon wool columns. In the absence of a herpetic infection the thymidine incorporation and macrophage migration inhibition responses to herpes simplex virus (HSV), Candida albicans and PPD, and the thymidine incorporation induced by PHA were functions of T cells. When a herpetic infection was present, the unfractionated lymphocyte response to HSV was increased, as measured by thymidine incorporation, but the T cell response was unchanged. However, T cells did show an increased response to HSV when prepared by elimination of cells forming rosettes with zymosan-complement. T cells of some patients were stimulated by contact with zymosan, and this correlated with the response to C. albicans. It is suggested that lymphocyte responses to HSV in man are mediated by T cells, but that these cells are specifically retained by nylon wool columns at the time of a herpetic infection. This may be associated with acquisition of an Fc receptor by the sensitized T cells.     

The nylon wool adherence marker of the B cell lineage appears at the resting pre-B cell stage

The proliferative state of functionally defined populations of size-separated pre-B cells was investigated. The results presented here support the hypothesis that pre-B cells are in the G₂ phase when stable membrane IgM is first expressed. Small resting precursor cells significantly adhere to nylon wool columns, unlike larger cycling cells which can be enriched in the nonadherent fraction. These results suggest that the nylon wool “receptor” is a useful early B cell marker. Since the in vitro recruitment of both cycling and resting precursors was shown to be essentially dependent on agar mitogen(s), cumulative data suggest that the receptors for agar mitogen(s) appear shortly before surface IgM on proliferating pre-B cells. Nylon wool adherence potential develops next on their resting progeny, followed by full lipopolysaccharide reactivity as cells further mature.     

Cytotoxicity of human peripheral blood and colostral leukocytes against Shigella species.

We examined the ability of human peripheral blood leukocytes to kill strains of Shigella sonnei and Shigella flexneri by using a modified bactericidal assay. Antibody-dependent cellular cytotoxicity (ADCC) was demonstrated in the presence of specific rabbit immune serum directed against S. sonnei. With peripheral blood leukocytes from adults, ADCC was found only in the mononuclear cell and purified lymphocyte populations. Monocyte-macrophages and polymorphonuclear leukocytes were unable to demonstrate ADCC. Lymphocyte ADCC, which was not affected by the addition of phenylbutazone (an inhibitor of phagocytosis), was mediated by a non-T, Fc receptor-positive, HNK-1- cell. ADCC (using antiserum directed against virulent S. sonnei) was demonstrated against virulent S. sonnei but not against virulent S. sonnei or virulent S. flexneri. In contrast to leukocytes from adults, both mononuclear and polymorphonuclear cells from neonatal cord blood and from a patient with chronic granulomatous disease mediated anti-Shigella ADCC. Breast milk leukocytes (BMLs) collected 1 to 3 days postpartum were used as effector cells against virulent S. sonnei. The entire BML population, BMLs which did not adhere to plastic and BMLs which passed through nylon wool columns mediated both natural killer cytotoxicity and ADCC. In paired experiments, natural killer cytotoxicity and ADCC were significantly lower (30 to 45% inhibition) but not ablated, when phenylbutazone was added to BMLs and nylon wool-purified BMLs (P less than 0.05). These experiments suggest that colostral leukocytes mediated both extracellular and intracellular bacteriolysis in the presence and absence of specific antiserum. These mechanisms may be active in vivo in protection against shigellosis.     

The role of soluble protein A in chicken spleen cell activation

Soluble protein A (SpA) caused chicken spleen cell proliferation despite considerable evidence that SpA has no binding affinity for avian immunoglobulin (Ig). This biological activity was examined by several approaches. SpA-stimulated spleen cell cultures demonstrated no difference in proliferative responses regardless of the addition of human gamma globulin (HGG) or keyhole limpet hemocyanin. Adsorbents composed of HGG or hemoglobin were equally ineffective in abrogating the ability of SpA to induce spleen cell proliferation. In addition, ion exchange purified SpA was observed to induce comparable levels of spleen cell proliferation as ion exchange-affinity purified preparations. The lymphocyte subpopulation responsible for the observed proliferative response to SpA resides in the nylon wool adherent population. Nylon wool nonadherent lymphocytes failed to proliferate to SpA, but did proliferate in response to phytohemagglutinin as did nylon wool adherent cells. These data indicate that SpA is not responsible for the observed biological activity and suggest that components from Staphylococcus aureus other than SpA copurify during the preparation of SpA and are responsible for the activation of spleen cells.     

Surface properties of lymphocyte subpopulations in autoimmune NZB/NZW F1 hybrid mice: alterations correlated with the immunodeficiency of aging

Partitioning in a two-polymer aqueous phase system was used to probe the surface properties of lymphoid cell subpopulations in aged male NZB/NZW F1 hybrid (B/W) mice, an important model of autoimmunity, immunodeficiency, and lymphoid malignancy. Spleen cells were fractionated by countercurrent distribution (CCD, a multiple-step extraction procedure) in a charged dextran-polyethylene glycol system. CCD of spleen cells from young, clinically normal male B/W mice yielded several broad distribution patterns which frequently had two or more peaks. Analysis of differentiation antigens and functional properties of cells from different parts of the distribution revealed a subfractionation of the three major lymphocyte subpopulations. B lymphocytes had a low partition coefficient (K); T cells had an intermediate K and null cells had the highest K. To examine the partitioning behavior of T lymphocytes, spleen cells which were nonadherent to nylon wool columns were subjected to CCD. Nonadherent cells from young B/W mice consistently gave a single peak with high K. Aged mice (18 months) usually had nonadherent cells with a predominantly low K. In some experiments a systematic increase in the number of these cells could be demonstrated with increasing mouse age. An analysis of the adherence and partitioning behavior of lymphocyte subpopulations revealed no change in the adherence properties or proportions of B lymphocytes in aged mice. The large proportion of cells having a low partition coefficient in the nonadherent spleen cell population of old mice appears to be due to an increase in the number of null cells and in a decrease in the K of some T lymphocytes.     

Strain difference of delayed-type hypersensitivity to BCG and its genetic control in mice.

Delayed-type hypersensitivity to BCG was remarkably different in two inbred strains of mice, SWM/Ms and C3H/He, when measured by the spleen index, the disappearance of peritoneal macrophage, or the footpad reaction. High responsiveness in the SWM/Ms strain appeared to be dominant over low responsiveness in the C3H/He strain. Results of the footpad reaction test if F1, F2, and backcross hybrids of these two strains of mice suggested that the delayed-type hypersensitivity was mainly controlled by a gene which was transmitted under Mendel's laws and was possibly non-H-2 linked. The spleen cells and their nylon wool nonadherent fraction from BCG-infected C3H/He mice were not reactive to purified protein derivative in vitro, whereas both the spleen cells and the nylon wool nonadherent fraction from BCG-infected SWM/Ms mice reacted well to purified protein derivative. Possible mechanisms of the different responses in the delayed-type hypersensitivity to BCG were discussed.     

Leukocyte subpopulations which amplify or suppress antigen-induced proliferation in Syrian hamsters

The proliferative response of spleen cells, obtained from Syrian hamsters sensitized to hen egg albumin emulsified in complete Freund's adjuvant, is lower in magnitude than the response of draining lymph node cells. In this study, the cellular regulatory mechanisms which may lead to splenic hyporesponsiveness were examined. Although unfractionated spleen cells were not suppressive, the addition of nylon wool nonadherent normal spleen cells to sensitized draining lymph node (target) cells markedly suppressed antigen- but not mitogen-induced proliferation. Suppressor cell activity was not detected in normal lymph nodes. Suppression could be overcome by culturing splenic suppressor plus target cell mixtures in the presence of large quantities of antigen. Suppressor cell activity was radioresistant. In addition to nonadherent suppressor cells, the hamster spleen also contains an adherent cell population(s) which amplified antigen-induced proliferation. Adherent cells with amplifying activity were also present in lymph nodes. The addition of adherent cells abrogated splenic suppression of proliferation. Collectively, these data indicate that the hamster spleen contains both suppressive and amplifying leukocyte subpopulations which may be involved in the regulation of the immune response to certain antigenic stimuli.     

Induction, isolation and surface marker studies on bovine eosinophils.

A crude extract from Ascaris suum was infused into the teat canal of heifers to serve as an irritant or an antigens. The cells present in the mammary gland following such stimulation were assessed over a period of 2 weeks. Prior to stimulation there were few cells, predominantly macrophages, however, by 12 h post-stimulation a larger number of eosinophils and neutrophils were present. The eosinophils, which represented approximately 50% of the total population, could be purified by Ficoll-Hypaque flotation and nylon or glass wool column filtration to yield a population consisting of over 90% eosinophils. Surface marker studies on the purified eosinophils revealed that they contained both Fc and complement receptors.     

Humoral inhibitors of the immune response in uremia. V. Induction of suppressor cells in vitro by uremic serum.

The mechanism of inhibition of mixed lymphocyte reaction (MLR) by serum of chronically uremic rats has been studied. The inhibitory activity of the serum has been associated with a discrete subset of very low density lipoproteins (VLDL) of Sf 100-400. The degree of the inhibitory activity of uremic serum correlates with the severity of uremia. Spleen cells from normal rats incubated for 20 hours with uremic serum or its VLDL fraction suppress the response of control syngeneic cells in the MLR. Induction of such suppressor activity does not require cell proliferation because it is not inhibited by mitomycin C. although the exact identity of the induced suppressor cells has not been established, they may be macrophages. The suppressor activity of induced spleen cells can be markedly reduced by filtration of spleen cells on glass wool or on nylon wool columns. Reconstruction experiments show that the adherent cell fraction of spleen cells exposed to uremic serum suppresses the response of the nonadherent fraction of control spleen cells. These results indicate that the immunosuppressive effects of rat uremic serum in vitro involve the induction of suppressor cells.     

Shedding and synthesis de novo of Fc and C3b receptors by cultured guinea-pig macrophages.

Resident macrophages freshly obtained from the peritoneal cavity of guinea-pigs were demonstrated to form a higher percentage of Fc and C3b rosettes than elicited macrophages when low concentrations of IgG and IgM-C3b were used to sensitize ox red blood cells (ORBC) in rosette assays. Culture of the total resident and elicited macrophages for 6 h at 37 degrees C resulted in a decrease of Fc and C3b rosette-forming cells, the loss of Fc receptor-bearing cells by resident macrophages only being apparent when using a sub-optimal concentration of sensitizing IgG. After 24 h incubation the percentages of Fc and C3b rosettes returned to their initial values. In contrast, there was no decline in the percentage of Fc and C3b rosettes formed by the adherent population of resident and elicited macrophages cultured for 6 h. However, extending the incubation of the adherent macrophage to 24 h produced an increase of Fc receptor-positive cells and a dramatic decrease of C3b receptor-positive cells. Culture supernatants of the total macrophage population that had been incubated for 6 h inhibited Fc and C3b rosette formation by freshly obtained elicited macrophages. These results, together with the demonstration that treatment of the total macrophage population with cycloheximide led to an inhibition of Fc and C3b receptor expression after 24 h culture, suggest that the Fc and C3b receptors of guinea-pig macrophages are shed and synthesized de novo during short-term culture. This system could be applied to the study in vitro of soluble immunoregulatory mediators on macrophage functions which are dependent on the expression of Fc and C3b receptors.     

Modulation of antitumoral antibody-dependent cellular cytotoxicity and natural killer activity by Adriamycin and daunorubicin

Mouse effector cells isolated from various anatomical sources failed to mediate antibody-dependent cellular cytotoxicity (ADCC) against alloantiserum-coated L1210 murine leukemia cell targets, whereas rat spleen cells appeared to be potent mediators of this activity. Following suppression of effector cell function 3 days after a single drug injection, the nylon wool non-adherent population of rat spleen cells from daunorubicin (DM)-treated rats demonstrated an increased ability to mediate ADCC compared to controls. Alternatively, although suppression occurred at day 7, no rebound enhancement was demonstrated by the same cell population isolated from Adriamycin (AM)-treated animals for as long as 12 days post-injection. Natural killer (NK) activity, measured as the ability of the nylon wool non-adherent rat spleen cell population to lyse uncoated L1210 cells, was modulated by drug treatment in a similar manner at each time point although the changes were not significant. In contrast to NK cells for which a substantial amount of activity remained adherent to nylon wool, all K cell activity was found in the non-adherent spleen cell population. The effector cell, in both cases, was not susceptible to antithymocyte serum plus complement treatment; however, NK activity appeared trypsin-sensitive whereas K cell activity did not. Therefore, AM and DM demonstrated different activities with regard toin vivo modulation of antitumoral ADCC.Supported in part by PHS Grant 5T32 GM07230 and a grant from the National Cancer Institute.     

Nonspecific cytotoxic cells in fish (Ictalurus punctatus). III. Biophysical and biochemical properties affecting cytolysis

Nonspecific cytotoxic cells (NCC) from the catfish (Ictalurus punctatus) may comprise a population of cells that are responsible for cellular immunity in the fish. NCC kill a wide variety of transformed target cells, and previous studies have indicated that NCC share properties with mammalian natural killer cells. In the present study, many biophysical and biochemical properties of NCC were defined. NCC were nylon wool nonadherent and adherent. NCC activity was also enriched in plastic nonadherent cells. NCC were nonphagocytic (for carbonyl iron), and they did not bind to Sephadex G-10. Characterization of NCC by density gradient centrifugation indicated that they comprise a relatively homogenous population of cytolytic cells that band at 45.5% Percoll. Moderate to high doses (500-2500 R) of X-irradiation produced a stimulatory effect on NCC lysis of labeled target cells. Additional studies indicated that a soluble suppressor protein in catfish serum (CFS) regulated NCC activity. This S. aureus protein A binding component isolated from CFS suppressed NCC activity. Analysis by SDS-PAGE indicated that the soluble regulatory protein had properties similar to immunoglobulin. These data indicate that NCC share some biophysical properties with mammalian natural killer cells. In addition, NCC appear to be under partial cell regulation by a radiation sensitive suppressor cell and also by a soluble regulator serum immunoglobulin component.