Critical Relationships Between Constituents of the Antigen-Adjuvant Emulsion Affecting Experimental Allergic Encephalomyelitis in a Completely Susceptible Mouse Genotype

Abstract

The production of EAE in the fully susceptible BSVS mouse genotype has been found to be dependent on the ratio of proteolipid antigen and adjuvant mycobacterial concentration as used in the emulsion, of the Freund type. Disturbance of this ratio, by manipulation of either component, by diminution or increase, results in a decrease in the frequency by which EAE is produced. Simultaneous reduction of antigen and mycobacteria, so that the ratio remains unchanged, retains the full EAE-producing power of the emulsion. The limit of this has not been ascertained. Emulsifying agents have been found to restrict further the permissible limits of the antigen-mycobacterial ratio for full EAE production. Such effects of the emulsifier have been found to vary with the qualitative nature of the emulsifier. Aquaphor has been found to be less restrictive than falba. These phenomena, systematically analyzed here for the mouse, may have an application for other antigen-adjuvant systems and for other hosts.

Mycobacterium smegmatisExpressing a Chimeric Protein MPT64-Proteolipid Protein (PLP) 139–151 Reorganizes the PLP-Specific T Cell Repertoire Favoring a CD8-Mediated Response and Induces a Relapsing Experimental Autoimmune Encephalomyelitis

“…A role for this type of pathogen has been suggested by studies from Harkiolaki et al (5), showing that peptides derived by microbial pathogens stimulate a T cells from a mouse transgenic for a TCR specific for DR2-MBP85-99. In the present report, we show that a self-reactive disease of the CNS can develop after a transient infection with a nonpathogenic Mycobacterium in the periphery, which results in appropriate stimuli leading to the development of the encephalitogenic phenotype in responding T cells (15).…”

“…Average duration of disease remission (calculated from the first day in which disease score was 1 point below the maximum value reached during the acute bout to the first day in which disease score had gained 1 point above the lowest value observed during remission) was 17. Induction of EAE by immunization with peptide depends on the dose of both peptide and adjuvant (15). To examine the effect of dose of infecting bacterium on the development of EAE, we conducted a second experiment with three groups of SJL mice, infected with 10 6 (6 mice) or 4 3 10 6 (six mice) or 4 3 10 7 (five mice) CFU of rMS p139 .…”

“…In the SJL mouse, EAE follows immunization with p139 alone without administration of pertussis toxin, indicating that p139-specific T cells primed in the periphery acquire a phenotype sufficient for homing into the CNS without need for alteration of the BBB. The development of EAE is critically dependent on the presence and amount of Mycobacterium tuberculosis products in the adjuvant (15) that provide nonantigenic moieties, thereby determining the encephalitogenic phenotype during priming. We therefore wondered whether infection with nonpathogenic mycobacteria carrying a determinant cross-reactive to CNS would trigger EAE, without need for presence of the infectious agent in the CNS.…”

“…Therefore, M. smegmatis has been used as vaccine vector, because it activates DCs and induces CD8-mediated immune responses (22)(23)(24)(25). Finally, killed M. smegmatis has been shown to provide the same adjuvant activity of M. tuberculosis during induction of EAE (15).…”

Prevention of Experimental Allergic Encephalomyelitis (Eae) by Vitamin C Deprivation

“…The fact that tuberculin sensitivity is also suppressed by scurvy is consistent with the autoimmune theory of EAE development. The recovery of tuberculin sensitivity following restitution of vitamin C, however, may indicate only that the mechanisms underlying tuberculin sensitivity are much cruder than those underlying the development of EAE, which depends upon a rather fine balance between concentrations of CNS and mycobacteria (4,9).…”