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Biomedical subjects

E C Lattime

Publications and source records attributed to E C Lattime.

11 recordsLinked to original sources
PubMed1992

Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells.

Intravesical administration of Bacillus Calmette-Guérin (BCG) is the most effective therapy for superficial transitional cell carcinoma of the bladder although its mechanism of action is not known. To determine if bladder tumors are capable of antigen presentation and thus might interact directly with BCG-specific T-cells, we studied the murine bladder tumor MB49. MB49 (MHC Class II negative) (IA-), when induced to express IA with interferon, presented BCG to specific CD4+ T-cells obtained from bladder-draining lymph nodes following intravesical BCG administration. This interaction resulted in antigen- and IA-dependent interleukin 2 and tumor necrosis factor production. Interferon also induced MB49 IA expression in vivo. This first demonstration of antigen presentation by epithelial tumors supports new approaches to immunotherapy of these malignancies.

Administration, Intravesical↗
PubMed1991

Thymic lymphomas mediate non-MHC-restricted, TNF-dependent lysis of the murine sarcoma WEHI-164.

Tumor necrosis factor (TNF), lyses a range of sensitive tumor targets and has been shown to be the mediator of natural cytotoxic (NC) activity first described in our laboratory. In this report, we identify two thymic lymphoma cell lines which lyse the prototype NC target WEHI-164 and share characteristics of NC. R1.1E and L5178-27av lyse the WEHI-164 sarcoma in 18-hr 51Cr release assays via a TNF-dependent, non-MHC-restricted (R1.1E) mechanism although they do not constitutively produce TNF. NC- and TNF-resistant variants of WEHI-164 are resistant to lymphoma-mediated lysis. Expression of the ganglioside GD3 by the lymphomas correlates with their relative levels of lysis. Thus, GD3, which is known to have a role in T cell activation may be involved in recognition or triggering for TNF-dependent cell-mediated lysis.

Animals↗
PubMed1989

Tumor growth in vivo selects for resistance to tumor necrosis factor.

The relationship between in vivo tumor growth and resistance to TNF in WEHI-164 cells has been examined. When a highly TNF-sensitive clone of WEHI-164 was grown in vivo in syngeneic mice it became resistant to rTNF such that a 4 to 5 log higher concentration of TNF was required to produce tumor lysis in vitro. When compared with an in vitro selected TNF-resistant variant, the in vivo selected line was significantly more tumorigenic. The resistant phenotype of both the in vivo and in vitro selected variants was stable in culture and both selected lines were also resistant to lysis by syngeneic spleen cells with natural cytotoxic activity. The parental clone and the two variants were equally sensitive to lysis by allo-CTL and expressed similar levels of MHC class I Ag. Resistance to TNF in the two variants was not a function of de novo production of TNF measured as supernatant TNF activity or TNF mRNA expression. These studies are the first to demonstrate that in vivo tumor growth results in resistance to TNF and therefore may have direct relevance to the efficacy of TNF in the treatment of human neoplasms.

Animals↗
PubMed1988

Human natural cytotoxic activity mediated by tumor necrosis factor: regulation by interleukin-2.

Freshly obtained normal lymphoid cells kill certain tumor target cells in vitro. Using peripheral blood lymphocytes (PBLs) and the human tumor target cell line BT-20, we have defined a tumor necrosis factor (TNF)-dependent, cell-mediated cytotoxic mechanism that is homologous to the murine natural cytotoxic (NC) cell activity. Human NC cell activity was detected in freshly isolated PBLs and was augmented by short in vitro pulses with recombinant human interleukin-2 but not with recombinant human alfa interferon. Monoclonal anti-TNF antibodies inhibited the killing of the target cells. The independence of interferon and the mediation of killing by TNF distinguish human NC cell activity from natural killer and lymphokine-activated killer cell activities.

Cells, Cultured↗
PubMed1985

Specific neonatally induced tolerance to Mls locus determinants.

Neonatal injection of CBA/HT6T6 (H-2k, Mlsb) mice with adult, Mls-incompatible (CBA/J [H-2k, Mlsd] X CBA/HT6T6)F1 spleen cells results in the abrogation of cell proliferation and interleukin 2 (IL 2) production in bulk mixed lymphocyte cultures, when spleen cells from the inoculated mice are tested at 6 to 8 wk of age with stimulator cells expressing the Mlsd of the tolerizing inoculum. In limiting dilution assays, this tolerant state was manifested in a 25- to 550-fold (280-fold average) decrease in the frequency of precursors of Mlsd-responsive IL 2-producing T cells. Tolerance was specific in that the frequencies of precursors of IL 2-producing cells responding to Con A, allogeneic H-2d, and self-Ia were not affected. The observed low frequency of Mls-responsive cells was due neither to extensive chimerism resulting in the dilution of Mlsd-responsive cells by the nonresponsive F1 cells of the inoculum, nor to the action of suppressor cells. These findings indicate that neonatal injection of Mls-incompatible spleen cells produces a state of specific tolerance by a clonal deletion or inactivation mechanism. This specific tolerance supports the view that 1) the Mls locus encodes or regulates the expression of defined alloantigenic determinants and 2) Mls-incompatible responder mice have specific receptors for Mls determinants on clonally distributed IL 2-producing responder T cells.

Animals↗
PubMed1978

l-Bunolol and propranolol: oral and intravenous beta-adrenoceptor blocking activity in rats compared to dogs and humans.

To determine the pharmacological significance of reported differences between species in l-bunolol metabolism, oral and intravenous beta-adrenoceptor blocking activity against an isoproterenol-induced tachycardia was compared in dogs, rats, and humans. Propranolol was similarly studied in rats and dogs. Species differences in intravenous potency were minimal for both compounds in contrast to oral dose studies. Oral to intravenous ratios of doses causing a comparable degree of beta-adrenoceptor blockade after l-bunolol were: rat, 212; dog 4; and human, 5. For propranolol, the oral to intravenous dose ratios were 210 and 32 for the rat and dog, respectively. These pharmacological findings show major differences in the rat compared to dogs and humans and may be explained in part by differences in the urinary excretion patterns of l-bunolol in the various species.

Administration, Oral↗
PubMedDate not supplied

WEHI-164 clone 2F: in vitro antitumor effects of tumor necrosis factor and gamma-interferon.

Based on their enhanced susceptibility to tumor necrosis factor (TNF), sublines of the BALB/c fibrosarcoma WEHI-164 are more and more frequently being used to measure levels of TNF in cell-free supernatants. In studies aimed at characterizing the cytostatic and cytolytic effects of TNF and gamma-interferon (IFN-gamma) on a highly TNF-sensitive subline of WEHI-164, we show that: (1) the MTT assay which measures viable cell numbers (i.e. both cytostasis and cytolysis) at appropriate target cell numbers is sensitive to less than 0.1 pg/ml of recombinant murine TNF (rmTNF) without the need to add protein synthesis inhibitors such as actinomycin D; (2) using irradiated cells, the MTT assay is significantly more sensitive and measures cell lysis but not stasis; (3) clone 2F is sensitive to the cytostatic, but not cytolytic effects of recombinant murine IFN-gamma; (4) although lysis of 2F by rmTNF requires more than 5 h, a short exposure (30-60 min) to rmTNF is sufficient to trigger the lytic process, and (5) lysis of 2F is not cell-cycle-dependent. The use of highly sensitive indicator cell lines such as 2F allow for the measurement of low levels of TNF present in culture supernatants and for studies into the mechanism of action of TNF. However, sensitivity to other agents such as IFN supports the need to confirm that the antitumor effects seen are due to TNF via neutralizing antibody.

Animals↗