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Biomedical subjects

P Erb

Publications and source records attributed to P Erb.

At least 73 records · Page 4Linked to original sources
PubMed1986

Association of symptomatic human infection with Toxoplasma gondii with imbalance of monocytes and antigen-specific T cell subsets.

During recent symptomatic toxoplasmosis, alterations in quantity and function of mononuclear cells in peripheral blood were observed. Flow cytofluorometric analysis and differential leukocyte counts revealed increased absolute numbers of T8+ cells, Leu 7+ (natural killer/killer) cells, and monocytes. T4+ cells and HLA-DR+ cells were not significantly changed. T4/T8 cell ratios were reversed in symptomatic toxoplasmosis (0.7 +/- 0.3) and normal in chronic infection (1.7 +/- 0.5). Toxoplasma antigen induced higher numbers of T8+ and TQ1+ cells in four T cell lines from two individuals with symptomatic infection than in five T cell lines from three individuals with asymptomatic infection. Eight cloned T cell lines produced gamma interferon in an antigen-specific fashion and in higher amounts when they originated from an asymptomatic subject than from a symptomatic subject. These results indicate that marked alterations in properties of immunoregulatory cells are characteristic of recent symptomatic toxoplasmosis. The transient immune dysfunction may be a major part of the observed disease and/or a feature of successful parasitism.

Acute Disease↗
PubMed1986

Spleen and lymph node cell populations, in vitro cell proliferation and interferon-gamma production during the primary immune response to Toxoplasma gondii.

An animal model for the study of transient lymphadenopathy-splenomegaly during toxoplasmosis is presented. Injection of CBA/J mice with the low virulent, cyst-forming strain of Toxoplasma gondii (Pe strain) induces a three to four fold increase in weight and cellularity of spleen and lymph nodes with peak changes at 30-50 days after infection. The spleen displays marked haemopoiesis, a 30 fold increase in mononuclear phagocytes, and a two fold increase in Lyt2+ lymphocytes. Lymph nodes show a five fold increase in mononuclear phagocytes and a four and a half fold increase in Lyt2+ T cells. The increase in mononuclear phagocytes significantly alters T cell/macrophage ratios and this is associated with decreases in in vitro cell proliferation to mitogen and toxoplasma antigen. The relationship between alterations in cell balance of mononuclear phagocytes and T cell subsets and the expression of transient immune dysfunction can now be examined by modulating changes in these cell types.

Animals↗
PubMed1986

In vitro cultivation of Toxoplasma gondii cysts in astrocytes in the presence of gamma interferon.

Long-term culturing of Toxoplasma gondii cysts was accomplished in vitro in association with murine astrocytes and intermittent additions of gamma interferon to the media. Phase-contrast microscopy was used to follow the stages of cyst development, and electron microscopy confirmed the presence of morphologic characteristics of T. gondii cysts. T. gondii cysts formed in vitro had a single trilaminar membrane during both intracellular and extracellular existence and contained amorphous electron-dense material either throughout the cyst or in a uniform layer under the trilaminar membrane. The bradyzoites were similar to previous descriptions of tachyzoites in vitro except that they were smaller and contained numerous electron-lucent vacuoles. Gamma interferon is not necessary for cyst formation, but it controls the division of tachyzoites and may allow cysts to remain for prolonged periods without rupturing. In vitro-cultivated T. gondii cysts will be useful for producing bradyzoite and cyst antigens and for measuring the effects of antimicrobial agents and immune modulators on the viability of intracystic T. gondii.

Animals↗
PubMed1985

Evaluation of accessory cell heterogeneity. I. Differential accessory cell requirement for T helper cell activation and for T-B cooperation.

Several Ia+ tumor cell lines and peritoneal exudate macrophages were tested as accessory cells (AC) for the activation of antigen-specific T cells and for T-B cooperation. The macrophages and all the Ia+ tumor lines tested induced the release of lymphokines from T cells in a major histocompatibility complex (MHC)-restricted fashion and reconstituted the antibody responses of AC-depleted spleen cells or of purified T and B cells. However, only the normal macrophages but none of the tumor lines induced carrier-specific T helper (Th) cells which help B cells for specific antihapten antibody responses by linked recognition. For T-B cooperation accessory cells were also required, but in contrast to Th cell activation any type of Ia+ AC (e.g. macrophage or tumor line) was effective. Strong MHC-restriction between the lymphocytes and the AC was seen if antigen-pulsed AC were added into the AC-depleted T-B cooperation cultures. If the AC and antigen were concomitantly added to the AC-depleted T-B cultures, MHC-restriction was less obvious. Concanavalin A supernatant reconstituted the response of AC-depleted T-B cultures provided antigen-specific Th cells and the hapten-carrier conjugate were present. If, however, tumor line-activated T cells were added instead of macrophage-induced Th cells, no cooperation with B cells took place even in the presence of Con A supernatant. The results obtained demonstrate a differential AC requirement for the induction of Th cells depending on the differentiation stage of the Th cells.

Animals↗
PubMed1985

Evaluation of accessory cell heterogeneity. II. Failure of dendritic cells to activate antigen-specific T helper cells to soluble antigens.

The activation of antigen-specific T cells requires Ia+, antigen-presenting accessory cells (AC). Dendritic cells (DC) and macrophages (M phi) isolated from spleen an peritoneal exudate were tested as AC for the activation of the activation of T helper cells and the induction of T cell proliferation. The cell separations to obtain DC and splenic M phi were performed by discontinuous bovine serum albumin gradients, adherence on petri dishes and rosetting with opsonized sheep erythrocytes. DC as well as the M phi were able to induce antigen-specific T cell proliferation, but only the M phi and not the DC activated antigen-specific T helper cells which help B cells for antibody production to soluble antigens. Keyhole limpet hemocyanin-specific T cells repeatedly stimulated with DC and antigen also did not express helper activity. The failure of DC to induce T helper cells was not due to the activation of a suppressor pathway. Thus, dendritic cells, although very efficient as AC in the induction of various T cell functions, are not able to activate T helper cells required for carrier-specific T-B cooperation and therefore cannot be the sole accessory cells. Based on these results and on previous data using Ia+ tumor cell lines as AC, we confirm the existence of functional AC heterogeneity.

Animals↗
PubMed1985

Ia determinants on macrophages.

It is well established that T cells cannot be activated by antigen alone but only if antigen is presented in context with I region associated (Ia) determinants. As a matter of fact, antigen-presenting cells or accessory cells, which are obligatory for the induction of any type of immune response, all share the same major characteristic of Ia expression. Thus, there seems to be a direct correlation between accessory cell function and Ia expression. Originally, Ia determinants were only detected on a few cell types, B cells and macrophages being the first. However, during the course of time, more and more cells were found to be Ia positive (Ia +) and it is possible that most cells can express Ia, if appropriately induced. The regulation of Ia expression has been best studied in macrophages, where it has been found that positive induction elements include phagocytosis and gamma-interferon, while prostaglandin E and alpha-fetoprotein tend to down-regulate the expression of Ia. The regulation of Ia expression on accessory cells is thus an integrated part of immune regulation. It is highly likely, although not yet directly proven, that the Ia molecules are the products of the immune response (Ir) genes located within the major histocompatibility complex. They may even be the mediators of the Ir genes which determine whether an immune response can take place at all and/or the extent of the response. Recently, it has been shown that not all Ia + cells are able to activate every known T cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Evaluation of accessory cell heterogeneity. III. Role of dendritic cells in the in vitro activation of the antibody response to soluble antigens.

Dendritic cells and macrophages obtained from spleen and peritoneal exudate were tested as accessory cells for the activation of lymphokine production by T cells, for supporting T-B cooperation and for the induction of antigen-specific T helper cells. Dendritic cells as well as macrophages were able to activate T cells for interleukin-2 secretion and functioned as accessory cells in T-B cooperation, but only macrophages induced T helper cells, which cooperate with B cells by a linked recognition interaction, to soluble antigens. Dendritic cell- and antigen-activated T cells also did not help B cells in the presence of Con A supernatants which contained various T cell- and B cell-stimulatory factors. The failure of dendritic cells to differentiate memory into functional T helper cells, but their efficient accessory cell function in T-B cooperation, where functional T helper cells are already present, can be best explained by a differential accessory cell requirement for T helper cell activation dependent on the differentiation stage of the T helper cell.

Animals↗
PubMed1983

Differentiation markers and accessory function of murine macrophages derived from cultured bone-marrow stem cells.

Murine bone-marrow cells cultured in the presence of colony-stimulating factor from mouse-lung-conditioned medium give rise to macrophages which function as accessory cells in antigen-specific T helper cell induction. Virtually all Ia+ bone-marrow stem cell-derived macrophages express determinants encoded in the I-A subregion. A second set of macrophages bears I-A as well as I-E/C-endoced determinants. The products of the I-A and I-E/C subregion, but not those of the I-J subregion, are involved in T helper cell induction.

Animals↗
PubMed1983

Evaluation of Ia+ tumor cell lines and peritoneal exudate macrophages as accessory cells: differential requirements for the activation of certain T cell functions.

Several Ia+ (BC3A, TA3, D1B) or Ia-inducible (WEHI-3, P388D1) tumor lines were tested for accessory cell function for the activation of antigen-specific T cell proliferation and for the induction of T helper cells that help B cells in antibody production. All lines were able to induce antigen-specific T cell proliferation in an MHC-restricted way, but none activated T helper cells to soluble antigens under all conditions tested. In comparison, starch-induced peritoneal exudate macrophages induced T cell proliferation as well as T cell help. Some of the lines tested induced nonspecific suppressor cells that were Ly-2-positive and partially or completely inhibited antibody responses. The induction of suppressor cells, however, is not the reason for the failure of the tumor lines to activate T helper cells. These data indicate that antigen-specific T cell proliferation and helper activity do not necessarily correlate.

Animals↗
PubMed1982

Association of specific immune response to pork and beef insulin with certain HLA-DR antigens in type 1 diabetes.

To test the association of HLA-DR antigens with high-responder and low-responder status to either beef or pork insulin, insulin antibodies in diabetic sera were separated into those with average low and those with average high affinity and their insulin-binding capacities for each insulin determined. Significantly less binding of pork insulin by the high affinity antibodies occurred in the group of patients with DR3 antigens compared with those with DR4 antigens (p less than 0.01) and DR3/4 antigens (p less than 0.01). The difference in the binding capacity of beef insulin by the high affinity antibodies between the groups with DR3 and DR4 antigens was less pronounced but still significant. The high-responder status of DR3/4 antigens to pork insulin suggests that the gene or genes associated with HLA-DR4, and responsible for a high response to pork insulin, are dominant to genes associated with HLA-DR3 and a low response. If extended to human insulin and different HLA-DR and HLA-B antigen patterns, these finding should help in the therapeutic selection of the appropriate insulin and thus reduce the induction of an anti-insulin response in patients with diabetes.

Animals↗
PubMed1981

Nature of macrophage-T cell interaction in secondary helper cell generation in vitro. Genetic restriction of macrophage-T cell interaction, which determines T-B genetic restriction.

To investigate the histocompatibility requirements for the macrophage-T cell interaction in the secondary antibody response, splenic T cells from antigen (carrier)-primed F1 hybrid mice were restimulated in vitro with carrier-pulsed F1, parental or allogeneic macrophages. Surviving T cell were cocultured with hapten-primed F1 or parental "B cells" and restimulated with the appropriate hapten-carrier conjugate. The IgG antibody-forming cell response was then measured using a plaque assay. Mapping of the genetic restriction was performed by use of different strain combinations. T helper cells could be restimulated in the presence of macrophages only provided they shared the I-A subregion of the major histocompatibility complex with the F1 T cells frm F1 hybrids restimulated with parental or I-A-identical macrophages were shown to only cooperate with parental B cells of the same I-A haplotype as the macrophages used for restimulation. The defect was at the level of the macrophage, as addition of macrophages of the I-A haplotype used for the restimulation culture reconstituted ability of F1 helper cells to cooperate with the I-A-nonidentical B cells.

Animals↗
PubMed1981

Genetics of human T cell-monocyte interaction in helper cell induction.

The generation of human antigen-specific helper cells from unprimed peripheral blood lymphoid cells in tissue culture requires the presence of the appropriate number of blood monocytes. The role of the HLA complex in this cell interaction was investigated, by using HLA-type donors, and it was found that the monocytes had to share at least one HLA-DR specificity with the T cell donor. These experiments suggested that the genes controlling the macrophage-T cell interaction are closely associated or in linkage disequilibrium with the HLA-DR region.

Animals↗