The polymeric immunoglobulin receptor (pIgR) plays a crucial role in mucosal immunity against microbial infection by transporting polymeric immunoglobulins (pIg) across the mucosal epithelium. We report here that the human pIgR (hpIgR) can bind to a major pneumococcal adhesin, CbpA. Expression of hpIgR in human nasopharyngeal cells and MDCK cells greatly enhanced pneumococcal adherence and invasion. The hpIgR-mediated bacterial adherence and invasion were abolished by either insertional knockout of cbpA or antibodies against either hpIgR or CbpA. In contrast, rabbit pIgR (rpIgR) did not bind to CbpA and its expression in MDCK cells did not enhance pneumococcal adherence and invasion. These results suggest that pneumococci are a novel example of a pathogen co-opting the pIg transcytosis machinery to promote translocation across a mucosal barrier.

The role of secretory IgA in conferring cross-protective immunity was examined in polymeric (p)IgR knockout (KO) mice immunized intranasally with different inactivated vaccines prepared from A/PR/8/34 (H1N1), A/Yamagata/120/86 (H1N1), A/Beijing/262/95 (H1N1), and B/Ibaraki/2/85 viruses and infected with the A/PR/8/34 virus in the upper respiratory tract (RT)-restricting volume. In wild-type mice, immunization with A/PR/8/34 or its variant (A/Yamagata/120/86 and A/Beijing/262/95) vaccines conferred complete protection or partial cross-protection against infection, while the B-type virus vaccine failed to provide protection. The protection or cross-protection was accompanied by an increase in the nasal A/PR/8/34 hemagglutinin-reactive IgA concentration, which was estimated to be >30 times the serum IgA concentration and much higher than the nasal IgG concentration. In contrast, the blockade of transepithelial transport of dimeric IgA in pIgR-KO mice reduced the degree of protection or cross-protection, in parallel with the marked increase in serum IgA concentration and the decrease in nasal IgA concentration (∼20 and 0.3 times those in wild-type mice, respectively). The degree of the reduction of protection or cross-protection was moderately reversed by the low but non-negligible level of nasal IgA, transudates from the accumulated serum IgA. These results, together with the absence of the IgA-dependent cross-protection in the lower RT and the unaltered level of nasal or serum IgG in wild-type and pIgR-KO mice, confirm that the actively secreted IgA plays an important role in cross-protection against variant virus infection in the upper RT, which cannot be substituted by serum IgG.

No abstract

We have compared the cytolytic activities and the cellular compositions of the inal lntraeplthellal lymphocyte (i-IEL) populations in three different combinations of conventional (CV) and germ-free (GF) mice. Cytolytic activity of i-EELs exps yS T-l antigen receptors (TCRs) b strain dependent in CV mice (high vs. low), and this straindependent variability b unaltered in the GF condition. Although absolute numbers of yv i-IELs are sightly decrased, the composition of CD8aa+ and CD4-CD8-subsets and the usage of TCR r and 8-chain variable gene segments by yS i-EELs remain the same in GF mice. By contrast, cytolytic activity of ar TCR-expressing i-JELs is uniformly high in CV mice but attenuated sharply in the GF condltion. A conspicuous decrease in the total numbers of afl i-IELs is also noted, and CD8rP+ and CD4+CD8+ subsets are reduced, whereas the CD8aa+ subset is expanded in GF mice. These rults indicate that microbial deprivation preferentially influences the a,B i-EEL population to decrease and become noncytolytic but has little effect on the pd size or characteristics of yS i-EELs. Consequently, cytolytic activity of feshly isolated i-KELs from GF mce b determined by T cellsexp ng y8TCRs and is found to be strin dependent.

Bifidobacterium breve, included in fermented milk, was tested for adjuvanticity and mitogenicity using cells of mouse Peyer's patch, one of the gut-associated lymphoid tissues. Addition of B. breve enhanced antilipopolysaccharide antibody production in Peyer's patch cells and also anti-sheep red blood cell plaque-forming cells in Peyer's patch cells cultured with sheep red blood cells. Furthermore, addition of B. breve accelerated proliferation of Peyer's patch cells, particularly B cells. In BALB/c mice, enhancement of proliferation by B. breve was also found in Peyer's patch cells from nude mice and a B cell-enriched fraction, including both the B cell fraction and plastic-adherent cells. Enhancement was not found in the fraction in which Sephadex G10-adherent and carbonyl-iron phagocytic cells were excluded from Peyer's patch cells or in a pure B cell fraction in which plastic-adherent cells were excluded from the B cell-enriched fraction of Peyer's patch cells. The proliferation of B cells was enhanced when the supernatant of plastic-adherent cells cultured with B. breve was added. It is concluded that B. breve activated plastic-adherent cells and that these cells secreted a soluble factor that enhanced proliferation of B cells.