Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver

Background

The induction of sterile immunity and long lasting protection against malaria has been effectively achieved by immunization with sporozoites attenuated by gamma-irradiation or through deletion of genes. For mice immunized with radiation attenuated sporozoites (RAS) it has been shown that intrahepatic effector memory CD8⁺ T cells are critical for protection. Recent studies have shown that immunization with genetically attenuated parasites (GAP) in mice is also conferred by liver effector memory CD8⁺ T cells.

Findings

In this study we analysed effector memory cell responses after immunization of GAP that lack the P52 protein. We demonstrate that immunization with p52 ^-GAP sporozoites also results in a strong increase of effector memory CD8⁺ T cells, even 6 months after immunization, whereas no specific CD4⁺ effector T cells response could be detected. In addition, we show that the increase of effector memory CD8⁺ T cells is specific for the liver and not for the spleen or lymph nodes.

Conclusions

These results indicate that immunization of mice with P. berghei p52 ^-GAP results in immune responses that are comparable to those induced by RAS or GAP lacking expression of UIS3 or UIS4, with an important role implicated for intrahepatic effector memory CD8⁺ T cells. The knowledge of the mediators of protective immunity after immunization with different GAP is important for the further development of vaccines consisting of genetically attenuated sporozoites.     

Diorganotin(IV) compounds derived from n‐methyl‐2,2′‐diphenolamine and 2,2′‐diphenolamine

The reaction of N‐methyl‐2,2′‐diphenolamine 1 and 2,2′‐diphenolamine 2 with some diorganotin(IV) oxides [R1/2SnO: R¹ = Me, n‐Bu, t‐Bu and Ph] led to the syntheses of diorgano[N‐methyl‐2,2′‐diphenolato‐O,O′,N]tin (IV) 3–6 and diorgano[2,2′‐diphenolato‐O,O′,N]tin (IV) 7–9 . All compounds (except 7 ) studied in this work were characterized by ¹H, ¹³C, ¹¹⁹Sn NMR, infrared, and mass spectroscopy. Their ¹¹⁹Sn NMR data show that the tin atom is tetracoordinated in CDCl₃ but penta and hexacoordinated in DMSO‐d₆. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 133–139, 1999     

NMR study of the coordinating behavior of 2,6‐bis(benzimidazol‐2′‐yl)pyridine

The coordination sites of 2,6‐bis(benzimidazol‐2′‐yl)pyridine ( 1 ) toward protons and the diamagnetic metal ions Li⁺, Na⁺, and Co³⁺ were investigated by NMR spectroscopy. Variable temperature ¹H and ¹³C NMR experiments were performed on 1 in order to evaluate the tautomeric equilibrium and hydrogen bonding. Imidazole dicoordinated aromatic nitrogen atoms were protonated by trichloroacetic acid and the three N‐dicoordinated atoms by fuming H₂SO₄. Reactions of the ligand 1 and benzimidazole 2 with metallic sodium or LiH afforded anionic species; the alkali metal ions appeared solvated by THF, but not by the ligands 1 or 2 . In contrast, reaction of 1 with Co(III) produces the stable cation [Co( 1 ‐H)₂]⁺ with cobalt ion coordinated by two molecules of the monodeprotonated ligand. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:392–398, 2000     

The use of hydrophobic spacers in the development of new temperature- and pH-sensitive polymers

The preparation and characterization of two series of methacrylic acid derivative polymers is described. One series contains aliphatic spacers with one to ten methylene units, while the other series includes an aromatic ring with changes in the position of the acid, as spacer. Both series of polymers were obtained as methoxy-ester protected acid polymers and as polymers containing free acid groups in different amounts. pH-sensitive gels and temperature-sensitive N-isopropylacrylamide (NIPAAm) copolymers were prepared by using some of the monomeric structures described. The pH of the swelling transition of the gels changed from 3.5 up to 9.0 as a function of the spacer length and type. The lower critical solution temperature (LCST) of NIPAAm copolymers in water was lowered from 33.6°C to 6°C as a function of the co-monomer content and type. The observed changes in the pH of the swelling transition of gels and in the LCST of NIPAAm copolymers can only be explained if hydrophobic-hydrophobic and hydrogen-bonding interactions are considered in connection with the specific chemical structure of the monomers used.