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Biomedical subjects

C S Henney

Publications and source records attributed to C S Henney.

At least 73 records · Page 4Linked to original sources
PubMed1978

Natural killer cells. In vitro and in vivo.

A nonadherent, nonphagocytic mouse cell found in lymphoid organelles, but lacking characteristic surface markers of mature lymphocytes, is capable of lysing a wide spectrum of tumor cells but shows little cytolytic activity toward normal cells. This cytotoxic cell, termed a "natural killer" (NK) cell, shows a marked capacity to lyse lymphomas (syngeneic, allogeneic, or even xenogeneic) to the effector cell source. Its activity is inhibited by a variety of pharmacologic agents, eg, cytochalasins, cAMP-"active" drugs, and colchicine, over the same dose range at which these drugs inhibit other cytotoxic cells. We have no evidence that NK cell "specificities" are clonally distributed. Two sets of evidence are presented which suggest that the same NK cell population is responsible for lysing a variety of tumor target cells. Preliminary evidence suggests that modulation of NK cell levels in vivo is correlated with resistance to challenge with a syngeneic tumor, inferring that NK cells may play a salient role in host defenses against neoplasia.

Age Factors↗
PubMed1978

Liposomes as model membrane systems for immune attack. I. Transfer of antigenic determinants to lymphocyte membranes after interactions with hapten-bearing liposomes.

The interaction of human peripheral blood lymphocytes with liposomes containing DNP-aminocaproyl-phosphatidylethanolamine together with either egg yolk or dipalmitoylphosphatidylcholine has been investigated. When lymphocytes were incubated with liposomes at 37 degrees C, the aqueous compartment (86Rb+) and the lipid portion (3H-lipid) of the liposomes became cell associated to an equivalent extent. At 0 degrees C, however, the incorporation of 3H-lipid exceeded that of 86Rb+. Lymphocyte-liposome interactions were accompanied by the transfer of DNP to the surface of the lymphoid cell as measured by susceptibility to complement in the presence of anti-DNP antibody. Hapten transfer was not limited to liposome interactions with lymphocytes, but occurred also with other cells (e.g., Chang cells). Hapten transfer could also be demonstrated by susceptibility to K cell-mediated lysis. These findings suggest that liposomes may prove to be a useful vehicle for the transfer of new antigenic determinants onto cell surfaces. The implications of these findings are discussed in the context of using liposomes as targets for cell-mediated cytotoxic attack.

Animals↗
PubMed1977

Studies on the mechanism of lymphocyte- mediated cytolysis. VIII. The use of con A to delineate a distinctive killer T cell subpopulation.

Alloimmune spleen cells (C57BL/6 anti P815), but not normal spleen cells, lyse syngeneic (EL4) target cells in the presence of Con A. Con A dependent cytotoxicity was mediated by T cells and required the continued presence of lectin. Cytolysis in the presence of a succinylated derivative was equivalent to that seen with the parent Con A molecule. In contrast to previous reports of Con A dependent cytolysis, however, we conclude that lysis is not primarily caused by directly cytotoxic T cells. The reasons for this conclusion are: 1. Removal of directly cytotoxic cells by adsorption on P815 monolayers did not alter the Con A dependent cytolysis of EL4 cells; 2. Populations in which no direct T killers were demonstrable (e.g., spleen cells harvested 5 days after alloimmunization) lysed both P815 and EL4 cells in the presence of Con A; and 3. Con A dependent cytolysis, but not direct cytotoxicity, could be induced by culturing normal C57BL/6 spleen cells for 4 days with a sonicated extract of P815 cells. We hypothesize that the cell "activated" to lyse targets in the presence of Con A is a T cell which has differentiated lytic potential following alloantigenic stimulation, but has either insufficient density or affinity of antigen receptors to serve as a directly cytotoxic cell. The role of Con A is viewed as 2-fold: i) to "bridge" killer and target cell, and ii) to "activate" the effector.

Animals↗
PubMed1977

Studies on the mechanism of lymphocyte-mediated cytolysis. IX. Relationships between antigen recognition and lytic expression in killer T cells.

The relationship between antigen recognition and lytic expression by killer T cells was studied by co-culturing two effector cell populations. When antigen recognition was bidirectional (e.g., b anti-d cells cultured with d anti-b) there was a loss of lytic activity in both populations. In contrast, when antigen recognition was unidirectional (e.g., a anti-d co-cultured with d anti-b) then the loss of lytic activity only occurred in that direction; i.e., there was a marked decline in the d anti-b activity but no change in the a anti-d population. These studies suggest: i) that mere proximity to a killer cell does not lead to target cell death; ii) that accommodation of the T cell's antigen receptor is necessary for the cell to express its lytic potential; and iii) there is direct linkage between the T cell's antigen receptor site and its killing mechanism.

Animals↗
PubMed1977

The effects of neuraminidase and galactose oxidase on murine lymphocytes. I. Evidence for the differential delivery of signal(s) leading to cell proliferation and the differentiation of cytotoxic T cells.

The sequential treatment of normal C57BL/6 mouse spleen cell populations with neuraminidase (NA) and galactose oxidase (GO) resulted in cell proliferation, but not in the differentiation of cytotoxic T cells. In contrast, C57BL/6 spleen cells derived from animals primed 5 to 8 months earlier with alloantigen (P815 mastocytoma cells of the DBA/2 strain) both proliferated and demonstrated T cell-mediated cytotoxicity after NAGO stimulation. T cells differentiating into cytotoxic cells after NAGO treatment demonstrated properties similar to alloantigen-specific 'memory' T cells. These were: 1) cytotoxicity developed only from 'primed' cell populations, 2) cytotoxicity developed within 24 hr after NAGO treatment, 3) DNA synthesis was not required for the differentiation of cytotoxic cells during the first 24 hr of culture but both DNA synthesis and cell proliferation were required for the cytotoxicity developing after 24 hr, and 4) all cytotoxicity induced by NAGO showed specificity for the priming alloantigen. It was found, furthermore, that cytotoxicity could be induced at much lower GO concentrations than needed for increased DNA synthesis. We interpret this finding as an indication that NAGO can differentially deliver two 'signals' to T lymphocytes: one leading to cell proliferation, the other causing the differentiation of memory T cells into cytotoxic effectors.

Animals↗
PubMed1977

BCG-induced murine effector cells. II. Characterization of natural killer cells in peritoneal exudates.

The cytotoxic activity in peritoneal exudates harvested from C57BL/6 mice 4 to 6 days after they had received viable Bacillus Calmette-Guérin (BCG) organisms i.p. was associatee with a nonadherent, nonphagocytic cell. The cytotoxic cell lacked demonstrable surface immunoglobulin and Thy 1 antigen and bore no readily detectable Fc receptors. Lytic activity was labile at 37 degrees C and was diminished after trypsinization of the effector cells. Preincubating effector cells with immune complexes was without effect on lytic expression. These features make it likely that the cytolytic activity was associated with "natural killer" (NK) cells, previously described in unimmunized mouse spleens and mesenteric lymph nodes. Whether BCG induced "activation" of resident NK cells, the de novo production of NK cells, or "homing" into the peritoneum of cells normally resident in other lymphoid tissue is not known.

Animals↗
PubMed1977

Studies on the cytotoxic activity of human lymphocytes. II. Interactions between IgG and Fc receptors leading to inhibition of K cell function.

The inhibition of human K cell-mediated cytolysis by a variety of immunoglobulin preparations was studied. It was found that inhibition was not a simple function of IgG concentration but was dependent on the mode of immunoglobulin presentation. The relative inhibitory capacity of IgG preparations on a weight basis was as follows: cell associated Ig larger than or equal to immobilized immune complexes greater than insoluble immune complexes greater than soluble immune complexes greater than heat-aggregated Ig greater than monomeric Ig. These results imply that the inhibitory capacity of immunoglobulin is determined by ligand (Fc) multivalency. It was found that although interactions between immunoglobulin and Fc receptors occur at low temperatures, these interactions lead neither to lysis nor to K cell inactivation. A temperature-sensitive post-binding event was required both for lysis to occur and for K cells to be inactivated. These findings lead us to propose that an IgG-induced redistribution ("capping") of Fc receptors on the K cell surface may be required for cytolysis and for effector -ell inactivation.

Antigen-Antibody Complex↗
PubMed1976

Evidence for direct linkage between antigen recognition and lytic expression in effector T cells.

The relationship between antigen recognition and lytic expression by effector T cells was examined by coculturing two cytolytically active lymphoid cell populations. When antigen recognition between the populations could occur only in one direction, then cytotoxicity was expressed only in that direction and the population whose antigens were recognized lost its lytic activity. In contrast, the cocultured effector cell population fully maintained its lytic potential. This lack of reciprocal inactivation was taken as evidence that T-cell receptor accomodation by surface antigen is linked to the expression of cytolytic activity by effector T lymphocytes.

Animals↗