Neutrophil Oxygen Radical Production by Dialysis Membranes

The ability of different dialysis membranes to activate polymorphonuclearneutrophil oxygen radical production was investigated with chemiluminescence.All the six membranes, namely cuprophan, cellulose acetate,polycarbonate, polysulphone, polyacrilonitrile and polymethylmethacrylatewere able to interact with neutrophils and stimulate their oxygenradical production, the highest responses being seen with polyacrilonitrile,polymethylmethacrylate and polycarbonate. To analyse the roleof complement in this interaction, fresh plasma, heat inactivatedand zymosan-activated plasma were added: with fresh plasma oxygenradical production was stimulated on cuprophan, cellulose acetateand polysulphone, not modified on polycarbonate, and decreasedon polyacrilonitrile and polymethylmethacrylate. With heat-inactivatedplasma, the responses were decreased or abrogated on all themembranes except polycarbonate and polymethylmethacrylate, whereaswith zymosanactivated plasma similar responses to fresh plasmawere observed. In addition, when plasma was used to precoatthe membrane, cuprophan, cellulose acetate and polysulphonedisclosed an enhanced neutrophil oxidative burst, while precoatedpolyacrilonitrile and polymethylmethacrylate were less stimulatorythan uncoated membranes. In contrast the precoating of polycarbonatedid not modify oxygen radical production. These data suggestthat neutrophil activation occurs by direct membrane neutrophilinteraction. Plasmatic factors modulate this interaction butcomplement seems involved on cellulosic and polysulphone membranesonly. Therefore, it appears that oxygen radicals produced fromcontact of neutrophils with the dialysis membrane might playan initial and/or additional role in the events occurring atthe initiation of haemodialysis.     

Three Evaluation Methods of a Community Health Advocate Program

The title Community Health Advocate (CHA) is one of thirty or more titles used throughout the world for an indigenous outreach worker who is trusted and respected in his or her community and who serves as a bridge between peers and health professionals. In 1992, the Center for Healthy Communities in Dayton, Ohio developed a program to train as Advocates people indigenous to the communities in which they would be working. Since the first CHAs began work in January 1993, the effectiveness of the program has been evaluated from three perspectives: the Community Health Advocates, the managers directors of the community sites at which the CHAs work, and the clients with whom the CHAs work. Advocates indicated that the training program adequately prepared them for their roles and functions. They also identified systematic frustrations and barriers that made it more difficult for them to perform their job. Community site directors and community leaders indicated that the CHAs were considered a positive force in meeting client needs and facilitating independence, and were very effective in outreach and coordination of resources. A survey of CHA clients revealed an overwhelmingly positive response to the Advocate's work, validating the belief that CHAs can fill an important niche in the health care community. The three evaluation processes described in this paper helped to document the need for and the effectiveness of this program and can serve as a model for similar programs.     

Enhancement of immunogenicity of Jeg3 cells by ectopic expression of HLA-A*0201 and CD80

PROBLEM: The choriocarcinoma cell line Jeg3 suppresses immunity in vitro by secretion of soluble factors like leukemia inhibitory factor suppressing leukocyte activation. The cells lack expression of classical human leukocyte antigen (HLA)-A and -B alleles but express some HLA-C, and non-classical HLA-G and -E. Upon binding to killing inhibitory receptor on natural killer (NK) cells, HLA-G prevents activation of cytolytic activity. We investigated whether Jeg3 cells are capable of immune stimulation after complementation with classical HLA and T cell costimulatory signal CD80. METHOD OF STUDY: Jeg3 cells were transduced to express HLA-A*0201 and/or CD80. Parental Jeg3 or transfectants Jeg3-A2, Jeg3-CD80 or Jeg3-CD80-A2 were used to stimulate allogeneic resting and activated peripheral blood lymphocytes (PBL). The different cell lines were loaded with a HLA-A2-restricted Epstein-Barr virus (EBV) recall antigen peptide epitope and antigen presenting ability was examined. T cell lines specific for Jeg3 and transfectants were generated from HLA-A2 matched and nonmatched donors and compared for expansion, phenotypes and cytolytic activity. RESULTS: While all Jeg3 cell lines induced only marginal proliferation of resting T cells, phytohemagglutinin (PHA)-activated T cells were stimulated by CD80 or CD80-A2 expressing Jeg3. Only the transfectant Jeg3-CD80-A2 was capable of specific T cell stimulation by EBV recall antigen presentation. T cell lines of HLA-A2 non-matched donors stimulated with the Jeg3 transfectants showed significant expansion only when HLA-A2 and the costimulus CD80 were present. T cells from HLA-A2 positive donors did not expand significantly or differentially. No NK cells grew under any condition. In Jeg3-CD80-A2 stimulated T cells lines CD8+ cells expanded preferentially. These T cells exerted cytolytic activity toward all Jeg3 cell lines. CONCLUSION: Our data suggest that, in spite of immunosuppressive mechanisms, proliferative and cytolytic T cell responses are induced by Jeg3 cells when classical HLA- and/or costimulatory signals are present on the cells.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.