Delayed-type hypersensitivity to allogeneic mouse epidermal cell antigens. III. Analysis of suppressor cells

The specificity of suppressor T cells (Ts cells) induced by intravenous administration of allogeneic spleen cells was studied in mice using a delayed-type hypersensitivity (DTH) assay. The DTH responses were induced by subcutaneous injection of allogeneic epidermal cells (ECs) and were assayed by footpad swelling. Afferent-phase Ts cells (Ts-aff cells) were transferred into the recipient mice before ECs immunization. Treatment with monoclonal anti-Thy-1.2 antibody and complement abolished the suppression by Ts-aff cells in the DTH response. The suppression induced by Ts-aff cells, however, was resistant to the treatment with monoclonal anti-I-A or anti-Lyt-2.2 antibody and complement. These results showed that Ts-aff cells were Lyt-2-, Ia- T cells. Efferent-phase Ts cells (Ts-eff cells) were transferred before challenge of the DTH assay. Phenotypic analysis of these Ts-eff cells showed them to be Lyt-2+, Ia- T cells. Studies using several strains of congenic mice revealed the antigen specificity of both Ts cell subsets. Adoptive transfer of Ts-eff cells required H-2 restriction, but Ts-aff cells did not. We also induced cognate suppression of the DTH responses to the alloantigens mediated by Ts-eff cells.     

Composition of Dietary Fatty Acids and Health Risks in Japanese Youths

In the overall composition of dietary fatty acids (FAs), the quantity of each FA is interrelated with that of others. We examined the associations between dietary FA composition and cardiometabolic risk in Japanese youths. Risk factors (anthropometric characteristics, serum lipid and liver enzyme levels, and blood pressure) were measured in 5485 junior-high-school students. Dietary intake was assessed using a food frequency questionnaire. The mean saturated FA (SFA), monounsaturated FA (MUFA), omega-6 polyunsaturated FAs (PUFAs), and omega-3 PUFAs intake were 9.6%E, 10.3%E, 6.3%E, and 1.1%E, respectively. In compositional regression analysis controlled for confounders, a high intake of omega-6 PUFAs relative to others was associated with low low-density-lipoprotein cholesterol levels (LDL-C; p = 0.003), and relative SFA intake was associated with high levels of gamma-glutamyl transpeptidase (p = 0.019). Relative omega-3 PUFAs intake was associated with low blood pressure (p = 0.005–0.034) but had unfavorable effects on adiposity and alanine transaminase. Substitutional models showed similar results for omega-6 PUFAs on LDL-C, but MUFA had inconsistent effects on risk factors. The results from the compositional data analysis were consistent with previous studies and clinical practice/knowledge. Focusing on increasing omega-6 PUFAs in Japanese youths could have favorable consequences in the long term.     

New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.     

HIV-1-specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomes and inhibited by anti-interferon-gamma antibody.

The adjuvant effect of mannan-coated liposomes on human immunodeficiency virus type-1 (HIV-1) DNA vaccine and the mechanism of this enhancement were studied. Coating of cationic liposomes with mannan significantly enhanced the ability of this vaccine to induce an HIV-specific delayed-type hypersensitivity (DTH) response. HIV-specific cytotoxic T-cell (CTL) activity elicited by DNA vaccination was also significantly enhanced with the mannan-liposome cocktail. This mannan-liposome-mediated activity was greatly inhibited by in vivo injection of anti-interferon (IFN)-gamma antibody, which suggests that IFN-gamma plays an important role in this HIV-specific immune response. The results of both isotype-specific antibody and cytokine analysis revealed that mannan-liposome-mediated DNA vaccination enhances Th1-mediated immunity.     

Reversible proliferation arrest of rat 3y1 fibroblasts and selective killing of simian-virus transformed derivation of 3y1 by short-chain Fatty-acids

We examined the effect of saturated fatty acids with carbon number from 2 to 10 on proliferation and survival of rat untransformed fibroblast 3Y1 cells and its transformed derivation induced by Simian virus 40 (SV-3Y1). Acetic acid (C2) had no effect on proliferation of these cells. Among medium-chain fatty acids (C6-C10), caproic acid (C6) showed the lowest proliferation inhibitory effect. Caprylic (C8), pelargonic (C9), and capric acid (C10) exerted killing activity to both 3Y1 cells and SV-3Y1 cells, and the toxicity increased with the elongation of their alkyl chains. The toxicity was a little greater to 3Y1 cells than to SV-3Y1 cells. In contrast, short-chain fatty acids caused reversible proliferation arrest in 3Y1 cells at 25 mM in propionic (C3), 5 mM in butyric (C4) and 10 mM in valeric (C5) acids. These short-chain fatty acids arrested 3Y1 cells not only in the GI phase but also in the G2 phase of the cell cycle. To SV-3Y1 cells, however, these short-chain fatty acids were cytotoxic. The cytotoxicity to SV-3Y1 cells was the greatest in butyric acid among short-chain fatty acid tested. These results suggest that short-chain fatty acids exert ploliferation-arresting activity against normal cells while exerting killing activity to the transformed cells.     

Treatment of patients with metastatic gastric-cancer by continuous-infusion of 5-Fluorouracil, Cisplatin and Etoposide

The therapeutic effectiveness of continuous infusion of 5-fluorouracil and cisplatin, and etoposide (FEP) for treatment of metastatic gastric cancer was examined. Studies were made on 17 patients with gastric cancer with distant metastases. 5-fluorouracil (300 mg/m(2)/day) and cisplatin (80 mg/m(2)/day) were administered by continuous intravenous infusion for 120 and 24 hours, respectively; etoposide (60 mg/m(2)/day) was injected intravenously over a 2 hour period on days 2, 3 and 4. These chemotherapy treatments were repeated every 28 days. Partial, but not complete, remission was seen in four patients (24%). The treatment increased the survival times of patients with differentiated or Borrmann 2 or 3 type cancer, but not significantly. In many cases the treatment caused myelosuppression, but side effects were usually mild or moderate. It is concluded that infusion of 5-fluorouracil, etoposide and cisplatin is effective and well tolerated.