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T J Powell

Publications and source records attributed to T J Powell.

36 records · Page 2Linked to original sources
PubMed1990

Neonatal tolerance induction by class II alloantigens activates IL-4-secreting, tolerogen-responsive T cells.

Neonatally induced tolerance of class II MHC alloantigens in mice of the A/J strain background is achieved without evident clonal deletion, because lymphoid cells from tolerant animals proliferate in mixed lymphocyte reactions against tolerogen-bearing stimulators. However, the pattern of lymphokines produced in bulk cultures by these tolerogen-reactive cells is unusual in that, unlike lymphocytes from nontolerant normal mice, lymphocytes from tolerant mice produce measurable amounts of IL-4 when stimulated with tolerogen. Using limit dilution analysis, we have determined that the ability to detect IL-4 in bulk cultures is caused by a high frequency of precursors of Ag-specific IL-4 secreting (pIL-4) cells among tolerant, but not normal, responder lymphocytes. Moreover, after repeated in vitro exposure to class II alloantigens, and after in vivo grafting with class II-disparate skin, the frequency of pIL-4 cells rises among lymphocytes from normal mice, eventually reaching levels similar to those found in class II tolerant mice. Because in normal mice a high frequency of class II-reactive pIL-4 cells reflects the "primed" state, we conclude that a subset of T cells that resemble Th2 cells is similarly primed in neonatally tolerized mice. We propose that this priming is achieved by the neonatal inoculation of semiallogeneic bone marrow cells. Because no expansion in the clone size of tolerogen-specific precursors of Ag-specific IL-2-secreting T cells (pIL-2) is observed among tolerant animals, and because the pIL-2 cells from tolerant mice are incapable of differentiating into cytotoxic and delayed hypersensitivity effector cells, we further propose that the precociously primed pIL-4 cells function as "suppressor" cells, helping to maintain the tolerant state.

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PubMed1989

Induction of effective immunity to Moloney murine sarcoma virus using monoclonal anti-idiotypic antibody as immunogen.

We have isolated an anti-idiotypic mAb (RS1.1.3), which recognizes an idiotope present on several IgM mAb specific for Moloney murine leukemia virus (M-MuLV)-determined cell surface Ag. The binding of RS1.1.3 to idiotypic antibody could be inhibited by specific Ag. Intraperitoneal immunization of mice with purified RS1.1.3 antibody-induced effective immunity against Moloney murine sarcoma virus challenge. A single injection of RS1.1.3 7 days before virus challenge resulted in a 27% reduction in tumor load compared to non-immune control mice challenged with the same dose of virus, whereas multiple injections of RS1.1.3 before virus challenge resulted in a 75% reduction in tumor load. The protective effect of anti-idiotype immunization appeared to be T dependent, because immunization of athymic mice had no effect on their susceptibility to tumor virus challenge. Administration of the anti-idiotypic antibody after virus inoculation caused an increase in tumor load of nearly 50% compared to non-immune controls. BALB/c mice immunized with RS1.1.3 developed anti-anti-idiotypic antibodies, as well as M-MuLV Ag-specific antibodies. Analysis of sera from RS1.1.3-immune mice subsequently challenged with Moloney murine sarcoma virus indicated an inverse relationship between tumor load and M-MuLV-specific serum IgG titers induced by the RS1.1.3 immunization. These results indicate that anti-idiotypic mAb may be used as immunogen to induce Ag-specific antibody responses, and to cause effective immunity to a retro-virus-induced tumor.

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PubMed1989

Isotype distribution and specificity of the antibody response to primary Moloney murine sarcoma virus infection in BALB/c mice.

The development and isotype distribution of Moloney murine leukemia virus (M-MuLV)-specific serum antibodies following primary inoculation with Moloney murine sarcoma/leukemia virus (M-MuSV/M-MuLV) in adult BALB/c mice have been investigated using an enzyme-linked immunosorbent assay (ELISA). The primary antibody responses to M-MuSV/M-MuLV consisted of the IgM, IgG2a, IgG2b, and IgG3 isotypes; no M-MuLV-specific serum IgG1 or IgA antibodies were detected. The detectable antibody response was biphasic, with an early peak of virus-specific titers seen between 10 and 15 days after inoculation and a second peak seen in regressor sera. Pooled regressor sera contained IgM, IgG2a, and IgG2b antibodies which bound to M-MuLV-expressing lymphoma cells. Immunoelectron microscopy with regressor sera showed IgG bound both to infected cell surfaces and to mature viral particles, while IgM bound only to infected cell surfaces. These findings were supported by immunoprecipitation analyses which demonstrated binding of the M-MuLV-specific antibodies to both virion-associated and cell-associated antigens encoded by the gag and env genes.

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PubMed1988

Activation of a functional idiotype network response by monoclonal antibody specific for a virus (M-MuLV)-induced tumor antigen.

BALB/c mice were injected with IgM mAb specific for Moloney murine leukemia virus (M-MuLV)-determined cell surface Ag in an attempt to inhibit Moloney sarcoma growth. The monoclonal IgM significantly inhibited sarcoma growth when given to the mice after inoculation with Moloney murine sarcoma/leukemia virus, and also potentiated the in vivo antibody response specific for M-MuLV Ag. These responses were significantly greater than the primary response to the virus alone in age- and sex-matched control mice, and were also seen in mice which were injected with the IgM antibody only and not with virus, suggesting that an Ag-independent mechanism may be involved. The M-MuLV-specific serum antibody responses induced by the monoclonal IgM, with or without prior virus inoculation, were predominantly of the IgG1 isotype, with some IgG2a; no other isotypes were found to have titers significantly higher than in the normal response to virus alone. M-MuLV-specific IgG1 was detected only in mice injected with monoclonal IgM, and not in the response to virus alone. The same sera also had high titers of anti-idiotypic antibodies, (Ab2), as well as anti-anti-idiotypic antibodies (Ab3). It appears, therefore, that passive immunization with M-MuLV-specific IgM mAb activates an idiotypic network, which results in both Ab2 and Ab3 responses; the M-MuLV-specific response may be considered a subset of Ab3.

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PubMed1987

Monoclonal IgM antibodies that inhibit primary Moloney murine sarcoma growth.

Monoclonal IgM antibodies with specificity for Moloney murine sarcoma virus (M-MuSV)-Moloney murine leukemia virus (M-MuLV) from two hybridoma clones have been isolated and characterized. The monoclonal antibodies have specificity for a cytoplasmic and cell surface Friend-Moloney-Rauscher group-specific antigen. Immunoelectron microscopy revealed antibody binding to the surface of virus-expressing cells but not to the budding virus particles. Treatment of M-MuSV-injected mice with monoclonal IgM anti-M-MuSV significantly inhibited tumor growth compared to virus-inoculated animals receiving either saline or MOPC 104E. Nude mice exhibited delayed tumor induction following treatment with the monoclonal antibodies but ultimately died from tumor growth. Virus-injected euthymic mice that were treated with monoclonal IgM anti-M-MuSV generated a potentiated spleen cell-mediated cytotoxicity against Moloney sarcoma cells compared to virus-infected treated with saline. This potentiation of cytotoxicity remained after trypsinization of the spleen cells and thus was probably not due to passively adsorbed monoclonal antibody. The antibodies alone or in the presence of complement did not neutralize M-MuLV. The IgM antibodies induced specific tumor cell cytotoxicity in vitro mediated by complement spleen cells, lymph node cells, or thymus cells. In conclusion, two monoclonal IgM anti-M-MuSV antibodies that bind to the tumor cell surface did not neutralize virus can inhibit primary M-MuSV-induced tumor growth in vivo. The regression event appeared to involve heterogeneous mechanisms. Complete regression remained thymus dependent even with passive antibody therapy, but significant tumor growth inhibition was produced independent of T-cells. In vitro these IgM antibodies induced complement and cell-mediated cytotoxicity.

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PubMed1975

The use of self-help groups as supportive reference communities.

Self-help groups such as Recovery Inc., Parents without Partners, and Alcoholics Anonymous have a unique role in relation to the professional system of human services. From the professional's standpoint, such groups may be viewed as self-sufficient programs, concurrent treatment programs, and as sources of information and users of consultation. Patterns of influence operative in self-help groups are examined, and suggestions made for professional cooperation with such groups to the greater benefit of clients.

Group Processes↗
PubMedDate not supplied

Derivation of temporary emergency exposure limits (TEELs).

Short-term chemical concentration limits are used in a variety of applications, including emergency planning and response, hazard assessment and safety analysis. Development of emergency response planning guidelines (ERPGs) and acute exposure guidance levels (AEGLs) are predicated on this need. Unfortunately, the development of peer-reviewed community exposure limits for emergency planning cannot be done rapidly (relatively few ERPGs or AEGLs are published each year). To be protective of Department of Energy (DOE) workers, on-site personnel and the adjacent general public, the DOE Subcommittee on Consequence Assessment and Protective Actions (SCAPA) has developed a methodology for deriving temporary emergency exposure limits (TEELs) to serve as temporary guidance until ERPGs or AEGLs can be developed. These TEELs are approximations to ERPGs to be used until peer-reviewed toxicology-based ERPGs, AEGL or equivalents can be developed. Originally, the TEEL method used only hierarchies of published concentration limits (e.g. PEL- or TLV-TWAs, -STELs or -Cs, and IDLHs) to provide estimated values approximating ERPGs. Published toxicity data (e.g. lc(50), lc(LO), ld(50) and ld(LO) for TEEL-3, and tc(LO) and td(LO) for TEEL-2) are included in the expanded method for deriving TEELs presented in this paper. The addition here of published toxicity data (in addition to the exposure limit hierarchy) enables TEELs to be developed for a much wider range of chemicals than before. Hierarchy-based values take precedence over toxicity-based values, and human toxicity data are used in preference to animal toxicity data. Subsequently, default assumptions based on statistical correlations of ERPGs at different levels (e.g. ratios of ERPG-3s to ERPG-2s) are used to calculate TEELs where there are gaps in the data. Most required input data are available in the literature and on CD ROMs, so the required TEELs for a new chemical can be developed quickly. The new TEEL hierarchy/toxicity methodology has been used to develop community exposure limits for over 1200 chemicals to date. The new TEEL methodology enables emergency planners to develop useful approximations to peer-reviewed community exposure limits (such as the ERPGs) with a high degree of confidence. For definitions and acronyms, see Appendix.

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