Infection with<i>Mycobacterium bovis</i>BCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis

An experimental vaccine for enterotoxigenic Escherichia coli (ETEC) composed of a live, attenuated Salmonella vector-expressing enterotoxigenic E. coli fimbriae, colonization factor Ag I (CFA/I), stimulated a biphasic Th cell response when given orally and suppressed the normally produced proinflammatory response. Such suppression was also evident upon the Salmonella-CFA/I infection of macrophages resulting in diminished TNF-α, IL-1, and IL-6 production and suggesting that the CFA/I fimbrial expression by Salmonella may protect against a proinflammatory disease. To test this hypothesis, SJL/J mice were vaccinated with Salmonella-CFA/I construct 1 or 4 wk before induction of experimental autoimmune encephalomyelitis using an encephalitogenic proteolipid protein peptide, PLP139–151. Mice receiving Salmonella-CFA/I vaccine recovered completely from mild acute clinical disease and showed only mild inflammatory infiltrates in the spinal cord white and gray matter. This protective effect was accompanied by a loss of encephalitogenic IFN-γ-secreting Th cells and was replaced with an increase in IL-4, IL-10, and IL-13 secretion. Collectively, these data suggested that Salmonella-CFA/I is an anti-inflammatory vaccine that down-regulates proinflammatory cells and confers protection against a proinflammatory disease, experimental autoimmune encephalomyelitis, via immune deviation.

Section: Discussionsupporting

confidence: 81%

A Live Diarrheal Vaccine Imprints a Th2 Cell Bias and Acts as an Anti-Inflammatory Vaccine

Jun

Gilmore

Callis

et al. 2005

“…Furthermore, a Mycobacterium bovis strain bacillus Calmette-Guérin vaccine has been used to treat MS patients, and resulted in a significant reduction in lesions measured by gadolinium-enhanced magnetic resonance imaging (74). As further support of that notion, EAE can be prevented by prior injection of killed Tubercle bacillus (75,76) or infection with bacillus Calmette-Guérin (77). Infections stimulating a regulatory function in B cells can also protect from allergic diseases.…”

Section: Cd4mentioning

confidence: 68%

TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity

Lampropoulou

Hoehlig

Roch

et al. 2008

394

398

TLR sense microbial infections, and control activation of immune responses. Dendritic cells, macrophages, and B lymphocytes express TLR and the TLR-signaling adaptor protein MyD88. The impact of TLR-activated B cells on T cell-mediated inflammation is unknown. In this study, we have used mice carrying B cell-restricted deficiencies in MyD88 or in distinct TLR to examine the impact of TLR-activated B cells on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). We demonstrate that TLR-signaling in B cells suppresses inflammatory T cell responses (both Th1 and Th17), and stimulates recovery from EAE. Only certain TLR are required on B cells for resolution of EAE, and these are dispensable for disease initiation, indicating that a category of TLR agonists preferentially triggers a suppressive function in B cells and thereby limits autoimmune disease. The TLR agonists controlling the regulatory function of B cells are provided by components of Mycobacterium tuberculosis present in the adjuvant. Thus, MyD88 signaling in B cells antagonizes MyD88 signaling in other cells, which drives differentiation of Th17 cells and is required for induction of EAE. Altogether, our data indicate that B cells link recognition of microbial products via TLR to suppression of a T cell-mediated autoimmune disease.

“…Prevention of T1D in NOD mice exposed to the NKT cell ligand ␣-galactosylceramide has been linked to alterations in chemokine expression patterns and the preferential retention of transferred autoreactive CD8 ϩ T cells in the PLN (44). Likewise, transferred autoreactive CD4 ϩ T cells will accumulate within granulomas outside of the CNS in the protection from experimental autoimmune encephalitis associated with bacillus Calmette-Guerin infection (45). Furthermore, the importance of cell trafficking in governing autoimmune responses does not appear to be limited to T cells, because the control of migration into lymphoid follicles is an important point of regulation for autoreactive B cells (46).…”

Section: Discussionmentioning

confidence: 99%

Salmonella typhimurium Infection in Nonobese Diabetic Mice Generates Immunomodulatory Dendritic Cells Able to Prevent Type 1 Diabetes

Raine

Zaccone

Mastroeni

et al. 2006

Infection, commencing across a wide age range, with a live, attenuated strain of Salmonella typhimurium, will halt the development of type 1 diabetes in the NOD mouse. The protective mechanism appears to involve the regulation of autoreactive T cells in a manner associated with long lasting changes in the innate immune compartment of these mice. We show in this study that autoreactive T cell priming and trafficking are altered in mice that have been infected previously by S. typhimurium. These changes are associated with sustained alterations in patterns of chemokine expression. We find that small numbers of dendritic cells from mice that have been previously infected with, but cleared all trace of a S. typhimurium infection are able to prevent the development of diabetes in the highly synchronized and aggressive cyclophosphamide-induced model. The effects we observe on autoreactive T cell trafficking are recapitulated by the immunomodulatory dendritic cell transfers in the cyclophosphamide model.