The administration of bovine lactoferrin (LF) with 1 mg/g body weight before the murine cytomegalovirus (MCMV) infection completely protected the BALB/c mice from death due to the infection. In these LF-treated mice, a significant increase in the activity was found in the NK cells but not in the cytolytic T lymphocytes which recognized an MCMV-derived peptide. Moreover, the elimination of the NK cell activity by an injection with anti-asialo GM1 antibody abrogated such augmented resistance, thus supporting the hypothesis that the LF-mediated antiviral effect in vivo is performed through the augmentation of NK cell activity. No such LF-mediated antiviral effect in vivo with the increased NK cell activity was found in athymic nude mice, whereas it was restored completely by the transfer of splenic T cells from LF-treated donors. These findings therefore suggest that T lymphocytes induce both the augmentation of NK cell activity and the resultant antiviral effect in the LF-treated hosts.
Using fluorescent antibody techniques (FA) and light microscopy (LM) and electron microscopy (EM), this paper describes the morphological features of the ileum in the DK1 mouse orally challenged with adenovirus K87. At the peak of infection, virus is easily identified by FA in the epithelium of the villi and crypts of the ileum. LM shows that fluorescent cells have large, bizarre, uniformly basophilic nuclei containing deoxyribonucleic acid, as indicated by histochemical tests. EM further identifies these nuclei as belonging to columnar, goblet, or Paneth cells, all epithelial cells facing the lumen with a microvillus border. The basophilic material in the nuclei consists of virus particles 75 nm in diameter arranged in crystalline arrays. When found in the cell cytoplasm, the virions do not form arrays but are scattered or forn irregular aggregates, which may or may not be enclosed by single membranes. Infected columnar cells show mild cytopathic effects with no cell degeneration and necrosis, whereas the goblet and Paneth cells appear normal and maintain synthetic and secretory functions. All infected cells, however, share an abnormally accelerated extrusion rate, with columnar and goblet cells often being shed from the side rather than from the tip of the villi. The Paneth cells, which do not migrate out of the crypts, show a higher than normal rate of extrusion in the crypt lumen. Virus. Mouse adenovirus strain K87, isolated by Hashimoto (9), was used. The virus suspensions were prepared from freeze-thawed mouse kidney tissue cultures infected with the virus after five to nine passages through mouse kidney tissue cultures, as described in detail elsewhere (19). Viral challenge. The inoculum, 0.4 ml containing 4 x 105 50% tissue culture infective doses, was administered orally to each mouse under ether anesthesia through a metal tube inserted into the stomach. The control inoculum was 0.4 ml of physiological saline (10).
Intraepithelial T lymphocytes in the small intestine (IEL) consist of αβ T‐cell receptor (TCR)‐bearing T cells (αβ‐IEL) and γδ TCR‐bearing T cells (γδ‐IEL). Development and cytolytic activation of αβ‐IEL sharply attenuate in germ‐free (GF) mice fed a natural diet (Nat‐GF), but the number and cytotoxicity of γδ‐IEL are comparable between conventional (CV) and Nat‐GF mice. In this report, we compared the properties of IEL in Nat‐GF mice and GF mice fed antigen‐minimized diet (AgM‐GF mice) of C57BL/6 strain to evaluate an influence of gut antigenic load on IEL development. Numbers of αβ‐IEL and γδ‐IEL in AgM‐GF mice were less by 1.9‐ and 1.4‐fold than those in Nat‐GF mice, respectively. Significant decreases in the proportions of CD4+8−, CD4−8αβ+, and CD4+8+ subsets and a resultant increase in the ratio of CD4−8αα+ subset were evident in αβ‐IEL of Nat‐GF mice compared with CV mice, but the subset constitution of αβ‐IEL was similar between Nat‐GF and AgM‐GF mice. In contrast, relative composition of γδ‐IEL was not different between CV, Nat‐GF, and AgM‐GF mice. αβ‐IEL displayed low cytolytic activity in Nat‐GF mice and were almost deprived of their cytotoxicity under the antigen‐minimized condition. While γδ‐IEL were strongly cytolytic in Nat‐GF mice their cytolytic activity was remarkably reduced in AgM‐GF mice. These results indicate that γδ‐IEL are activated independently of microbial colonization in the gastrointestinal tract but their activation occurs in response to the exogenous antigenic substances other than live micro‐organisms.
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