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Biomedical subjects

S O Prather

Publications and source records attributed to S O Prather.

9 recordsLinked to original sources
PubMed1979

Inability of antiserum active in antibody-dependent cellular cytotoxicity and arming tests to protect against simian virus 40 tumor cell challenge.

Previous studies have shown that simian virus 40 (SV40) hamster tumor cells that were pretreated with antiserum from syngeneic hosts sensitized to SV40 were killed following exposure to nonsensitized spleen cells. In this study preincubation of nonadherent spleen or lymph node cells with SV40 antiserum rendered the cells specifically cytotoxic for the SV40-transformed fibroblasts. The capacity of a particular antiserum to "arm" (i.e., to be made specifically cytotoxic) was comparable with its ability to mediate antibody-dependent cellular cytotoxicity (ADCC). Experiments were performed to determine if the SV40 antiserum had prophylactic activity. Two hours after passive transfer of serum, cytotoxic effector cells could be demonstrated in the blood, spleen, and mesenteric lymph node, and the recipients' sera were active in ADCC tests. Nevertheless, such hosts were not resistant to challenge with small numbers of SV40 tumor cells that were given intradermally or intracardiacly, nor was tumor growth suppressed by addition of normal lymph node cells to the antiserum-pretreated tumor cell inoculum. Thus SV40 antiserum, active at high titer in ADCC and arming assays, did not prevent or delay growth of SV40 tumor isografts.

Animals↗
PubMed1977

Reversal of SV40 tumor-mediated suppression of spleen cell cytotoxicity by antibody.

Spleen cells obtained from hamsters bearing PARA-7 tumors greater than 1.0 cm were not reactive in microcytotoxicity assays unless preincubated overnight. The events occurring during in vitro incubation which lead to reversal of tumor-mediated suppression of cellular immunity were investigated. After 24 hr of incubation, supernatants overlying spleen cells from tumor-bearing hosts contained a factor which blocked cytotoxicity of simian virus 40 (SV40)3-sensitized spleen cells at the PARA-7 target cell level but not at the effector cell level. The preparations did not mediate antibody-dependent cellular cytotoxicity (ADCC). Opposite results were obtained in assays of culture medium overlying spleen cells from hosts with a tumor burden less than 0.1 cm. Although ADCC activity was present, no significant blocking was detectable. Treatment of inactive spleen cells with anti-hamster gamma-globlin in the presence of complement (anti-HGG + C) prevented activation and formation of blocking factor but did not impair the cytotoxic activity of already activated cells. Addition of SV40 antiserum to anti-HGG + C-treated cells led to effector cell activation, whereas heterologous virus-immune sera did not. Control studies established that the antibody-mediated recovery of cytotoxicity was not due to arming. Further studies showed that PARA-7 tumor antigen extract blocked at the effector cell level, not at the target cell level. Addition of PARA-7 extract to spleen cell supernatants mediating ADCC resulted in formation of a factor which blocked at the target cell level but not at the effector cell level. These data are compatible with the following interpretation. Spleen cell unresponsiveness is due to antigen blockade. Recovery of cytotoxicity occurs because antibody synthesized during the incubation period promotes elution of antigen from the effector cell surface. Thus, activation is accompanied by the generation of tumor antigen-antibody complexes.

Animals↗
PubMed1976

Membrane-associated antigen from the SV40-induced hamster fibrosarcoma, para-7. I. Role in immune complex formation and effector cell blockade.

PARA-7 membrane-associated antigen was prepared by treatment of the tumor cells with pH 9.4 glycine buffer, or by concentration of spent cell culture medium. When admixed with sensitized effector cells, both preparations could specifically block cellular cytotoxicity for PARA-7 target cells. Pretreatment of target cells with antigen did not result in blocking. Incubation of antigen extract with simian virus 40 (SV40) anti-serum caused neutralization of antibody-dependent cellular cytotoxicity (ADCC) with concomitant formation of a factor which blocked at the target cell level but not at the effector cell level. Serum from tumor-bearing hamsters exhibited blocking characteristics comparable to those of the antigen-SV40 teristics comparable to those of the antigen-SV40 antiserum preparation. Washing experiments indicated that PARA-7 antigen was more efficient than PARA-7 antigen-antibody complexes in blocking cell-mediated immunity in vitro. Material extracted from untransformed hamster embryo fibroblasts either by itself or when admixed with SV40 antiserum exhibited no significant blocking activity. These observations support the concept that loss of serum ADCC during progressive tumor growth is due to immune complex formation.

Animals↗
PubMed1976

Kinetics of serum factors mediating blocking, unblocking and antibody-dependent cellular cytotoxicity in hamsters given isografts of para-7 tumor cells.

Sera collected at intervals after PARA-7 tumor-cell inoculation were monitored for blocking, unblocking, and antibody-dependent cellular cytotoxicity (ADCC) using the microcytotoxicity test. Within 7 days after isografting, significant levels of blocking were demonstrated. This activity increased in parallel with tumor growth and reached a maximum at day 21. In contrast, the capacity of the sera to mediate ADCC was maximal at day 7, and no longer detectable at 3 weeks. Unblocking was not demonstrable in tumor-bearer sera. Further studies showed that, when the tumor was exicised, blocking activity fell rapidly while ADCC was elevated. Sera collected 7 days after surgery could neutralize the blocking activity of tumor-bearer sera. Significant levels of unblocking were still evident 10 weeks after surgery while ADCC had generally disappeared after 5 weeks. These findings illustrate the complexity of the hamster's humoral immune response to tumor cells, and suggest that (1) the sequestering of antibody by circulating tumor antigen accounts for the demise of ADCC in tumor-bearer sera and the concomitant appearance of blocking activity; and (2) the serum factors mediating ADCC and unblocking differ.

Animals↗
PubMed1975

Host-dependent restriction of mengovirus replication. II. Effect of host restriction on late viral RNA synthesis and viral maturation.

Restricted mengovirus replication in Mandin-Darby bovine kidney (MDBK) cells is characterized by a 400-fold reduction in infectious virus yield and a 40-fold increase in the production of noninfectious virus. Using conditions which insure that all MDBK cells are infected, virus-specific RNA and protein synthesis were measured in the restrictive host and in a permissive host for mengovirus, HeLa cells. Labeling kinetics and sucrose gradient analysis of mengovirus-specific RNA from MDBK cells show a reduction of 10-fold in virion RNA, 5-fold in double-stranded RNA, and 12.5-fold in single-stranded RNA. The viral RNA biosynthetic processes which occur late in the replicative cycle and result in the production of 90% of the single-stranded viral RNA that is packaged into capsid proteins in the permissive host are absent in restrictive MDBK cells. Viral protein synthesis as measured by labeled viral-specific polysome is decreased, and there is an accumulation of 80S subviral particles in the restricted host. It is suggested that restriction may act at a number of stages of viral replication and maturation.

Amino Acids↗
PubMed1975

Analysis of sera from SV40-immunized and tumor-bearing hosts for blocking activity and antibody-dependent cellular cytotoxicity.

The role of serum factors in tumor immunity to cells transformed by PARA-(defective SV40)-adenovirus 7 was investigated. It was found that sera from SV40-sensitized hosts did not block the specific cytotoxicity of SV40-sensitized spleen cells for PARA-7 cells. However, such sera could collaborate with nonsensitized spleen cells to produce specific killing. This activity could be absorbed out by PARA-7 cells but not by cells transformed by cytomegalovirus. The activity of sera from hamsters bearing tumor isografts depended upon when, after transplantation, the specimens were obtained. Sera collected greater than or equal to 10 days after grafting completely blocked immune spleen cell cytotoxicity and did not mediate target cell killing in the presence of normal spleen cells. Sera obtained at an earlier time, i.e., 3 to 6 days after transplantation, consistently were active in the antibody-dependent cellular cytotoxicity test and exhibited reduced or no blocking of antibody-independent cellular cytotoxicity. Thus, there appears to be an inverse correlation in the capacity of serum from tumor bearing hosts to block effector cell cytotoxicity and mediate antibody-dependent cellular cytotoxicity.

Absorption↗