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The difference in susceptibility to urinary tract infection between C3HIHeJ and C3H/HeN mice was tested for with gram-negative strains differing in lipopolysaccharide composition. Recently, impaired clearance of Escherichia coli from the kidney of C3H/HeJ compared to C3H/HeN mice was shown to be correlated with the LPS low responsiveness. In this study, a difference in clearance from the kidneys of C3H/HeJ and C3H/HeN mice was found only with lipopolysaccharide-containing bacteria. Gram-positive bacteria, e.g., Staphylococcus saprophyticus and Streptococcus agalactiae, were recovered in essentially equal numbers from the kidneys of mice of both strains. In contrast, of the lipopolysaccharide-containing strains used, all persisted in higher numbers in the kidneys of C3H/HeJ mice than in the kidneys of C3H/HeN mice. Variations in the 0 side chain did not eliminate this difference. E. coli Hu734 075+K5+ and the rjbmutant 075-K5+ remained in similar numbers in C3H/HeJ mice, although 075-K5+ was eliminated more rapidly in C3H/HeN mice. The core structure did not affect the differential persistence in the two mouse strains. The rjb mutants with R1-R4 cores were eliminated after 24 h from the C3H/HeN mice, but remained in significant numbers in the kidneys of C3H/ HeJ mice. Even the Re mutant of Salmonella minnesota persisted in low numbers in C3H/HeJ mice. The

The evidence of a specific bacterial cause of dental caries and of the function of the salivary glands as an effector site of the mucosal immune system has provided a scientific basis for the development of a vaccine against this highly prevalent and costly oral disease. Research efforts towards developing an effective and safe caries vaccine have been facilitated by progress in molecular biology, with the cloning and functional characterization of virulence factors from mutans streptococci, the principal causative agent of dental caries, and advancements in mucosal immunology, including the development of sophisticated antigen delivery systems and adjuvants that stimulate the induction of salivary immunoglobulin A antibody responses. Cell-surface fibrillar proteins, which mediate adherence to the salivary pellicle, and glucosyltransferase enzymes, which synthesize adhesive glucans and allow microbial accumulation, are virulence components of mutans streptococci, and primary candidates for a human caries vaccine. Infants, representing the primary target population for a caries vaccine, become mucosally immunocompetent and secrete salivary immunoglobulin A antibodies during the first weeks after birth, whereas mutans streptococci colonize the tooth surfaces at a discrete time period that extends around 26 months of life. Therefore, immunization when infants are about one year old may establish effective immunity against an ensuing colonization attempts by mutans streptococci. The present review critically evaluates recent progress in this field of dental research and attempts to stress the protective potential as well as limitations of caries immunization.

Oral tolerance, or systemic unresponsiveness to ingested antigen, was first described at the turn of the century; however, the underlying mechanisms involved have only recently been studied in detail (1). Several investigations (2-4) have shown that oral administration of sheep erythrocytes (SRBC) to'mice for prolonged periods results in systemic unresponsiveness to this antigen. The lack of responsiveness has been ascribed to T suppressor (Ts) cells (5), suppressor factors (3, 5), and immune complexes (2) in serum. Oral tolerance to soluble antigen has also been attributed to the induction of T8 cells in the gut-associated lymphoreticular tissue (GALT), e.g., Peyer's patches (6). The primary site for induction of IgA precursor cells to orally administered antigen is in GALT, e.g., Peyer's patches (PP), and the selective migration of these sensitized cells to secretory tissues constitutes a major pathway for immune responses at mucosal surfaces (7). The relationship between induction of IgA responses and oral tolerance is not clear; however, recent studies (8) have provided convincing evidence that oral administration of soluble or particulate antigen leads to concurrent induction of systemic unresponsiveness and secretory immunity. Our laboratory has shown (9) that high IgA immune responses to orally administered, thymic-dependent (TD) antigen occur in lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mice, and this response is due to enhanced production of T helper (Th) cells in GALT. If systemic unresponsiveness (oral tolerance) is mediated by Ts cells, which are induced in GALT, then the C3H/HeJ mouse may lack this cell type and thus offer a model for discriminating between T cell regulation of IgA immune responses and oral tolerance.We report that prolonged oral administration of SRBC to LPS-nonresponsive C3H/HeJ mice leads to heightened splenic responses to systemically administered antigen, whereas similar treatment of LPS-responsive mice results in oral tolerance. Tolerance was due to the induction of Ts cells, which occurred in both PP and spleen; however, this T cell effector pathway was not induced in C3H/HeJ mice. Materials and MethodsMice and Immunization. C3H/HeJ, C3H/HeN, BALB/c, and Swiss mouse strains were bred and maintained in the Core Facility for Immunocompromised Mice, The Comprehensive Cancer Center at the University of Alabama in Birmingham, Ala. Mice were 8-15 wk of age.SRBC (Colorado Serum Company, Denver, Colo.) were washed extensively and used for

We successfully cloned antigen-specific T cells from murine gut-associated lymphoreticular tissue, i.e., Peyer's patches, which are dependent upon T cell growth factor and independent of antigen for continuous growth. These clones exhibit helper activity for IgA responses to sheep erythrocytes (SRBC) and have been designated T helper (Th) A. Two broad categories of Th A clones have been maintained in continuous culture. The first group supports IgM and largely IgA anti-SRBC plaque-forming cell (PFC) responses in both normal and SRBC-primed splenic B cell cultures, whereas the second group supports low IgM, IgG1, and IgG2 and high IgA PFC responses. Subclones derived from single cells maintain the parent helper properties when propagated in culture for long periods (greater than 7 mo). Cloned Th A cells are antigen specific and do not support polyclonal or immune responses to other thymus dependent antigens in normal B cell cultures. Th A cells require full histocompatibility for helper functions because addition of cloned Th A cells to B cell cultures from other H-2 types does not result in IgA responses. Cloned Th A cells are Thy-1.2+ and Lyt-1+ and Lyt-2-, Ig-, and I-A-. Th A cells bear Fc receptors for IgA and do not possess receptors for IgM or IgG isotypes. Thus, T cells that primarily promote IgA isotype responses have been isolated in high frequency from murine PP, an anatomical site of major importance for induction and regulation of the IgA response.