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T M Ellis

Publications and source records attributed to T M Ellis.

At least 91 records · Page 5Linked to original sources
PubMed1992

Identification of a novel CD56- lymphokine-activated killer cell precursor in cancer patients receiving recombinant interleukin 2.

Circulating lymphokine-activated killer (LAK) cell activity in cancer patients receiving recombinant interleukin 2 (rIL-2) therapy is confined to cells expressing the CD56- surface marker. However, CD56- cells from these patients but not normal individuals have been reported to exhibit LAK cytotoxicity only following in vitro activation with rIL-2. Studies were performed to document the existence of CD56- LAK precursor cells and to phenotypically characterize this population in patients receiving rIL-2 therapy using fluorescence-activated cell sorter-purified CD56- cell subsets. Initial studies confirmed that CD56- cells exhibit NK activity [20 +/- 7 (SE) LU/10(6) cells] but not LAK activity (0 +/- 0 LU/10(6) cells) when evaluated directly from peripheral blood of patients receiving rIL-2. CD56- cells from patients but not normal individuals developed significant LAK cytolytic activity against NK-resistant COLO 205 targets (16 +/- 3 LU/10(6) cells) when cultured for 3 days with 1500 units/ml rIL-2. The CD56- LAK precursor activity was confined to cells expressing a CD56-CD16+ phenotype and a large granular lymphocyte morphology; little or no NK or LAK precursor activity was detectable in CD56-CD5+ T-cells from patients. Phenotypic characterization of CD16+CD56- cells revealed that this population is uniformly CD11a+,CD18+, and CD38+ and is heterogeneous in its expression of CD11b, CD11c, and CD16/Leu 11c. These results indicate that rIL-2 administration induces enhanced LAK precursor activity in a novel population of CD5-CD16+CD56- cells.

Antigens, CD↗
PubMed1992

Qualitative defects in natural killer cell function in ia osteopetrotic rats.

Recent studies have provided evidence that cells of the immune system and their associated cytokines function in the regulation of bone turnover. The incisors absent (ia) osteopetrotic rat represents a model in which a defect in the immune system and bone resorption can be studied. Osteopetrosis in the ia rat is characterized by a generalized excess accumulation of bone as a result of reduced bone resorption by defective osteoclasts that lack a ruffled border and the ability to exocytose their osteolytic enzymes. Previous attempts to identify associated defects in the ia immune system have proven unsuccessful; ia rats demonstrate normal delayed hypersensitivity, mitogenic activity, and macrophage function. Inasmuch as the skeletal manifestations of the ia mutation may be the result of a defect in exocytosis, related defects may be evident in immune cells utilizing exocytosis of granules or enzymes for their cytolytic function. Natural killer (NK) cells function by such a mechanism. Therefore, these studies were undertaken to evaluate the natural immune system in ia rats. NK activity assessed by 51Cr release assays was significantly reduced in ia animals compared to normal littermates. Mononuclear cells isolated from the peripheral blood of ia rats revealed a significantly greater percentage of large granular lymphocytes than normal littermates. Comparison of NK cell phenotypes using two phenotypic parameters for NK cells (OX8+, OX19- cells and 3.2.3+ cells) revealed that the mononuclear isolates of spleen and peripheral blood of mutant animals had significantly greater percentages of OX8+, OX19- and 3.2.3+ cells than normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Relationship between chronic ovine dermatophilosis and levels of T6 lymphocyte antigen staining in peripheral blood mononuclear cells.

Quantification of a T6-lymphocyte antigen in peripheral blood mononuclear cells of sheep was used to select 15 from 48 one year old Merino ewes not previously exposed to Dermatophilus congolensis infection. These sheep were compared in response to challenge with D. congolensis zoospores and levels of T-6 lymphocyte antigen in peripheral blood mononuclear cells with 15 Merino ewes of similar age and strain from a different site that had been treated and recovered from chronic dermatophilosis. The T-6 lymphocyte antigen levels were significantly lower in the chronic dermatophilosis sheep and they developed significantly more severe lesions than the selected, previously unexposed sheep despite the former sheep having high serum antibody levels to D. congolensis. Measurement of the fleece characteristics, wax and suint concentration showed no differences between the groups that might have explained the considerable differences in their susceptibility to dermatophilosis.

Actinomycetales↗
PubMed1991

Strain variation in Dermatophilus congolensis demonstrated by cross-protection studies.

Cross-protection studies were conducted with vaccines prepared from two isolates of Dermatophilus congolensis (designated strain 1 and strain 2). The vaccines were prepared as either heat-inactivated, washed, formalized filamentous phase bacterium, mixed with alum as an adjuvant, and inoculated intramuscularly (type A vaccine) or sedimented live filaments inoculated intradermally (type B vaccine). The vaccinated sheep were challenged with D. congolensis zoospores of one or other strain. Challenge sites were observed for the presence and severity of lesions. Serum antibody levels to D. congolensis were monitored after vaccination and challenge. Type A and B vaccines from both strains produced some reduction in the severity of lesions when sheep were challenged with strain 1 but not with strain 2. Unvaccinated control sheep developed more severe and persistent lesions when challenged with strain 2 than controls challenged with strain 1. Serum antibody levels to the type B vaccine prepared from strain 1 were significantly higher (P less than 0.05) than antibody levels to type B vaccine from strain 2. These findings showed there was significant variation in virulence and antigenicity between these two isolates of D. congolensis.

Actinomycetales↗
PubMed1991

Induction of human monocyte IL-1 mRNA and secretion during anti-CD3 mitogenesis requires two distinct T cell-derived signals.

The T cell signals that regulate the induction of human monocyte IL-1 during primary immune activation were investigated by using anti-CD3 mitogenesis. The induction of monocyte IL-1 alpha and beta mRNA during anti-CD3 mitogenesis was rapid (less than or equal to 1 h) and required the presence of both T cells and anti-CD3. The addition of T cells plus a nonmitogenic anti-CD5 antibody failed to induce IL-1 alpha or beta mRNA, indicating that IL-1 mRNA induction by anti-CD3 required T cell activation. Experiments using double chamber culture wells revealed that the major initial phase of IL-1 alpha and beta mRNA induction (1 to 12 h) required direct cell contact between monocytes and T cells. A subsequent minor late phase (greater than or equal to 12 h) of IL-1 mRNA was induced independently of cell contact in monocytes that received only soluble factors generated during anti-CD3 mitogenesis and was temporally associated with the appearance in culture supernatants of the late phase IL-1-inducing cytokines, IL-2, IFN-gamma, and TNF-alpha. Metabolic inactivation of T cells using paraformaldehyde demonstrated that the ability of T cells to induce IL-1 mRNA via cell contact was acquired only after activation of T cells via solid phase anti-CD3. Furthermore, pretreatment of T cells with the protein synthesis inhibitor emetine had no effect on T cell-mediated induction of monocyte IL-1 mRNA or cell-associated IL-1 alpha and beta, indicating that the expression of the IL-1 inductive signal did not require protein synthesis. Despite their ability to induce monocyte IL-1 alpha and beta mRNA, activated T cells treated with paraformaldehyde or emetine were no longer able to induce monocytes to secrete IL-1 beta into culture supernatants. However, supernatants from purified T cells that were activated with solid-phase anti-CD3 restored the ability of paraformaldehyde or emetine-treated T cells to induce IL-1 secretion. These studies provide evidence that supports a two-signal model of monocyte IL-1 production during primary immune activation. The first signal leads to the induction of monocyte IL-1 mRNA and is mediated by direct contact with activated T cells, and the second signal is provided by soluble T cell factors and results in IL-1 secretion.

Antibodies, Monoclonal↗
PubMed1991

Evaluation of vaccines against ovine dermatophilosis.

Intradermal vaccination of live crude filaments (vaccine A) was compared with a vaccine (vaccine B) consisting of a 45 kD zoospore protein and mucoid material coating filaments in its ability to protect sheep from experimental Dermatophilus congolensis infection. Fourteen and 21 days after challenge, vaccine A sheep had fewer lesions (P less than 0.001) than the vaccine B sheep. The lesions on the vaccine A sheep were also less severe 14 and 21 days after challenge (P less than 0.05, P less than 0.01 respectively). In a second study, vaccine A was assessed for its ability to protect against natural challenge. Ten weeks after contact with sheep with active and generalised dermatophilosis no difference was found between the number of lesions present on the vaccine A and unvaccinated sheep and no differences were found in the number of sheep in each group with active lesions.

Actinomycetales↗
PubMed1991

Evaluation of a toxoid for protection of rabbits against enterotoxaemia experimentally induced by trypsin-activated supernatant of Clostridium spiroforme.

Investigations were conducted into an enterotoxaemia caused by Clostridium spiroforme responsible for significant losses in commercial rabbit farms in Western Australia. Two trials using laboratory and farm bred rabbits were performed to evaluate the protective value of a toxoid prepared from the supernatant of C. spiroforme cultures against intraperitoneal challenge with the trypsin-activated toxin of C. spiroforme. The trials showed clearly that a single vaccination at weaning (four weeks) was protective against toxin but more complete and lasting protection was conferred following a second vaccination administered 14 days after the first. Adults likewise showed similar levels of protective antibodies but did not appear to pass on this protection to their kits although ELISA results indicated levels of antibody in kits from unvaccinated mother to be lower than progeny from vaccinated mothers. However antibody levels in kits from vaccinated mothers were very low and did not protect against challenge with toxin.

Animals↗
PubMed1991

The effect of antibody to caseous lymphadenitis in ewes on the efficacy of vaccination in lambs.

The effect of maternal antibody to the toxin of Corynebacterium pseudotuberculosis, produced by caseous lymphadenitis (CLA) in ewes or by vaccinating ewes before lambing, on the efficacy of vaccination against CLA in their lambs was examined. Lambs were allocated to treatments according to either the vaccination history of their dam or level of CLA toxin antibody of their dam. They were vaccinated twice using 2 different inoculation regimes and then artificially infected with CLA organisms. The number of lambs with CLA lesions was assessed at slaughter. In one experiment high levels of CLA toxin antibody activity in ewes were associated with decreased efficacy of CLA vaccination in their lambs, when lambs were vaccinated at 2 and 8 weeks or 8 and 14 weeks of age. In a second experiment the efficacy of lamb vaccination at 8 and 12 weeks, but not at 14 and 18 weeks of age, was decreased. In sheep flocks with a high prevalence of CLA, vaccinating lambs against CLA at less than 10 weeks of age may not produce optimum protection against CLA in lambs. There was no difference in infection rate between lambs from vaccinated and unvaccinated ewes. However, vaccination of lambs at 2 and 8 wks was less effective that vaccination at 8 and 14 weeks, probably due to reduced immunocompetence in young lambs. In sheep flocks where significant numbers of lambs receive their primary vaccination at less than 3 weeks of age vaccination programmes to control CLA in lambs may be less effective.

Animals↗
PubMed1990

Comparison of O-6-methylguanine DNA methyltransferase (MGMT) mRNA levels in Mer+ and Mer- human tumor cell lines containing the MGMT gene by the polymerase chain reaction technique.

O-6-Alkylguanine is a mutagenic and carcinogenic DNA lesion induced by a variety of alkylating agents, including the chloroethylnitrosoureas. The lesion is repaired by the alkyl-accepting suicide enzyme O-6-methylguanine DNA methyltransferase (MGMT). Approximately 25% of cell lines derived from human tumors are phenotypically deficient in this enzyme and are described as Mer-. Recent cloning of the human MGMT cDNA (Tano, K.; Shiota, S.; Collier, J.; Foote, R.S.; Mitra, S. Proc. Natl. Acad. Sci. USA 87:686-690; 1990) has allowed for a more detailed analysis of the basis of the Mer- phenotype in human Mer- tumor cell lines. Using the polymerase chain reaction (PCR) technique, an MGMT cDNA probe based on the published sequence was generated. The probe and the PCR technique were then used to analyze the presence and expression of the MGMT gene in two Mer+ and four Mer- lines, including one SV40-transformed Mer- line and three Mer- human tumor cell lines. The data demonstrate that while all six cell lines contained a relatively nonamplified, nonrearranged MGMT gene, Mer- lines contained levels of MGMT mRNA detectable only by PCR analysis. Of the three Mer- tumor cell lines examined, two (COLO 320 HSR, A1235) contained MGMT mRNA levels that were four to five orders of magnitude lower than that of the prototype Mer+ tumor line (HT-29), while one (BE) contained no consistently detectable MGMT mRNA. These results suggest that in the human Mer- tumor lines tested, the Mer- phenotype was mediated by a severe reduction in MGMT mRNA levels, despite the presence of the MGMT gene.

Base Sequence↗
PubMed1990

The impact of Hodgkin's disease on the immune system.

Patients with Hodgkin's disease, at presentation or in remission, exhibit a persistent defect in cellular immunity. Natural killer cell mediated cytotoxicity is depressed in untreated patients. Humoral immune function is transiently reduced following treatment. The cellular immune defect appears to be the result of enhanced sensitivity to suppressor monocytes and T-suppressor cells, in addition to abnormal interleukin-2 production. Patients with advanced disease have an inherent T-lymphocyte defect. Reed-Sternberg cells function as antigen-presenting cells for mitogen-induced and mixed lymphocyte T-cell proliferation.

Antibody Formation↗
PubMed1989

Induction of human lymphokine-activated killer cells by IFN-alpha and IFN-gamma.

By traditional definitions, NK cells can be activated by cytokines to exhibit two functionally distinct levels of cytotoxicity. Whereas IL-2-mediated activation of NK cells leads to the development of lymphokine-activated killer (LAK) cytotoxicity, characterized by the acquisition of cytolytic activity against NK-resistant targets, IFN-treated NK cells become activated without the acquisition of novel cytolytic specificities. In this study we show that NK cells activated by 18 to 24 h of stimulation with either IFN-alpha or IFN-gamma do acquire LAK cytolytic activity, demonstrated by the ability of IFN-treated PBMC to lyse NK-resistant COLO 205 cells as well as fresh tumor targets. The level of IFN-alpha-induced LAK activity was significantly greater than that induced by IFN-gamma, although IL-2-induced LAK activity was considerably greater than IFN-alpha-induced LAK cytotoxicity. Maximal IFN-induced LAK cytotoxicity occurred after 24 h of culture, and occurred with the use of IFN-alpha at 500 U/ml and IFN-gamma at 1000 U/ml. Whereas neutralizing antibody experiments demonstrated that IFN-alpha-induced LAK activation did not involve the participation of endogenously produced IL-2, the partial inhibition (63%) of IFN-gamma-induced LAK cytotoxicity by anti-IL-2 and of IL-2-induced LAK by anti-IFN-gamma (33.3%) indicates that the induction of LAK cytotoxicity by either of these individual cytokines involves the endogenous production and participation of the other cytokine. Similar to IL-2-induced LAK cells, phenotypic analysis revealed that IFN-alpha/gamma LAK cells were Leu-19+, although the Leu 19"dim"+ subset exhibited greater IFN-induced LAK activity than the Leu-19"bright"+ subset. The results of this study clearly demonstrate that IFN-alpha and IFN-gamma induce classic LAK activity and IFN-gamma plays a participatory role in the optimal induction of LAK cells by IL-2.

Cytotoxicity, Immunologic↗