Hanaa Y. Bakir

Essential Role of Extrathymic T Cells in Protection Against Malaria

Athymic nude mice carry neither conventional T cells nor NKT cells of thymic origin. However, NK1.1−TCRint cells are present in the liver and other immune organs of athymic mice, because these lymphocyte subsets are truly of extrathymic origin. In this study, we examined whether extrathymic T cells had the capability to protect mice from malarial infection. Although B6-nu/nu mice were more sensitive to malaria than control B6 mice, these athymic mice were able to survive malaria when a reduced number of parasitized erythrocytes (5 × 103 per mouse) were injected. At the fulminant stage, lymphocytosis occurred in the liver and the major expanding lymphocytes were NK1.1−TCRint cells (IL-2Rβ+TCRαβ+). Unconventional CD8+ NKT cells (Vα14−) also appeared. Similar to the case of B6 mice, autoantibodies (IgM type) against denatured DNA appeared during malarial infection. Immune lymphocytes isolated from the liver of athymic mice which had recovered from malaria were capable of protecting irradiated euthymic and athymic mice from malaria when cell transfer experiments were conducted. In conjunction with the previous results in euthymic mice, the present results in athymic mice suggest that the major lymphocyte subsets associated with protection against malaria might be extrathymic T cells.

PROTECTION AGAINST MALARIA DUE TO INNATE IMMUNITY ENHANCED BY LOW-PROTEIN DIET

Mice were fed ad libitum with a normal diet (25% protein) or low-protein diets (0–12.5% protein) for a wk and then infected with a nonlethal or lethal strain of Plasmodium yoelii, that is, blood stage infection. The same diet was continued until recovery. Mice fed with a normal diet showed severe parasitemia during nonlethal infection, but survived the infection. They died within 2 wk in the case of lethal infection. However, all mice fed with low-protein diets survived without apparent parasitemia (there were small peaks of parasitemia) in cases of both nonlethal and lethal strains. These surviving mice were found to have acquired potent innate immunity, showing the expansion of NK1.1−TCRint cells and the production of autoantibodies during malarial infection. Severe combined immunodeficiency (scid) mice, which lack TCRint cells as well as TCRhigh cells, did not survive after malarial infection of lethal strain of P. yoelii, even when low-protein diets were given. These results suggest that low-protein diets enhanced innate immunity and inversely decreased conventional immunity, and that these immunological deviations rendered mice resistant against malaria. The present outcome also reminds us of our experience in the field study of malaria, in which some inhabitants eventually avoided contracting malaria even after apparent malarial infection.

Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int B220+ γδ T cells with double-negative CD4 − CD8− phenotype in the liver

DBA/2 (H‐2d) mice are known to be more resistant than C57BL/6 (B6, H‐2b) mice to the non‐lethal 17XNL strain of Plasmodium yoelii. This is a very strange phenomenon because the functions of conventional T cells, especially CD8+ T cells, are known to be somewhat lower in DBA/2 mice than in other strains of mice. We examined herein how immune responses differed between DBA/2 mice and B6 mice during malarial infection. DBA/2 mice and (DBA/2 × B6)F1 (BDF1, H‐2b/d) mice were found to have milder parasitaemia and to recover more quickly from malarial infection than B6 mice. These DBA/2 and BDF1 mice were also found to experience a marked expansion of interleukin (IL)‐2Rβ+ CD3int cells and γδ T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220+ T cells) was also marked in DBA/2 and BDF1 mice. The majority of B220+ T cells were γδ T cells and these T cells were double‐negative CD4− CD8−. More importantly, the production of immunoglobulin M (IgM)‐type anti‐DNA autoantibody was also higher in DBA/2 and BDF1 mice than in B6 mice. In conjunction with data on cytokine production, these results indicate that primitive T and B cells, namely autoreactive extrathymic T cells and autoantibody‐producing B cells, may be much more activated in DBA/2 mice and therefore resistant to the non‐lethal 17XNL strain of P. yoelii.

Transient appearance of hepatic natural killer cells with high cytotoxicity and unique phenotype in very young mice.

There were few natural killer (NK) cells in the liver in very young mice at the age of 1–2 weeks. This was because the cell yield from the liver of young mice was low. The percentage of NK cells in the liver of young mice, however, was almost comparable with that in the liver of adult mice. Lymphocytes were isolated from the liver and spleen of C57BL/6 (B6) mice, and NK cytotoxicity and phenotype were herein examined in this study. NK cytotoxicity was extremely high in the liver of very young mice. This phenomenon was seen in the liver of various normal mouse strains. In contrast, the appearance of high cytotoxicity was not seen in NK cells of the spleen, irrespective of mouse strains. The quality of NK cells in the liver of young mice was different from that in adult mice. NK cells in the liver of young mice were mainly CD69+Mac‐1– Fas ligand+, whereas those in the liver of adult mice were CD69–Mac‐1+ Fas ligand–. These results revealed that the quality of hepatic NK cells changes in the process of ageing. Namely, liver NK cells in very young mice temporarily show the highest NK cytotoxicity and a unique activated phenotype. Physiological meaning of the present phenomenon was discussed.

Capillaria philippinensis in Upper Egypt: Has It Become Endemic?

The goal of this study was to present an overview of human infections with Capillaria philippinensis, a new emerging parasite in Upper Egypt. The study included 21 inpatients who had been admitted to the Assiut University Hospital. Patients suffered from intermittent abdominal pain, borborygmi, chronic diarrhea lasting for several weeks, and marked weight loss. Hypoalbuminemia and low serum levels of potassium, calcium, and sodium were detected in most patients. A stool examination was performed using direct smears and the formalin-ether concentration method. Intact adult worms and/or eggs were evaluated using a light microscope and processed for scanning electron microscopy. The examination by light microscopy illustrated the general morphology of different stages. Using scanning electron microscopy, intestinal villi were found partially covering the cuticle of the adult worms, which provided evidence for the invasion of adult worms into the jejunal mucosa. Two distinct types of eggs, thick-shelled and thin-shelled, were identified and measured.