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Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression.
J Immunol 1995; 155(2):910-6JI

Abstract

We have previously shown that orally administered myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis in both the Lewis rat and the SJL mouse. In the Lewis rat fed low doses of MBP, we found that protection can be adoptively transferred by CD8+ cells and that these cells inhibit immune responses via the secretion of TGF-beta after Ag-specific triggering. In the present study, we investigated the cellular requirements for the generation of active suppression following oral administration of MBP in SJL and (PLJ x SJL)F1 mice. We first determined the frequency of MBP cells secreting Th1 (IFN-gamma) and Th2 (IL-4/IL-10) cytokines or TGF-beta after oral administration of MBP. We found that in SJL mice, orally administered MBP (0.5 mg/feeding) led to an increased frequency of TGF-beta-, IL-4-, and IL-10-secreting cells and a decreased frequency of IFN-gamma-producing cells. This pattern was observed in both CD4+ and CD8+ populations; adoptive transfer of either CD4+ or CD8+ cells from orally tolerized mice suppressed autoimmune encephalomyelitis in recipient animals. We then studied the role of CD8+ cells on the generation of oral tolerance to MBP by depleting CD8+ cells in vivo with anti-CD8 mAb. Oral tolerance was successfully induced in such animals, as demonstrated by a decrease in clinical disease and T cell proliferative responses, although there was less TGF-beta production in vitro and less disease protection on days 20 to 22 in CD8-depleted animals. These studies demonstrate that CD4+ cells in the absence of CD8+ cells can mediate the active suppression component of oral tolerance in mice and that there is a reciprocal relationship between Th1- and Th2-type cytokine production associated with oral tolerization.

Authors+Show Affiliations

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7541826

Citation

Chen, Y, et al. "Induction of Oral Tolerance to Myelin Basic Protein in CD8-depleted Mice: Both CD4+ and CD8+ Cells Mediate Active Suppression." Journal of Immunology (Baltimore, Md. : 1950), vol. 155, no. 2, 1995, pp. 910-6.
Chen Y, Inobe J, Weiner HL. Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression. J Immunol. 1995;155(2):910-6.
Chen, Y., Inobe, J., & Weiner, H. L. (1995). Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression. Journal of Immunology (Baltimore, Md. : 1950), 155(2), pp. 910-6.
Chen Y, Inobe J, Weiner HL. Induction of Oral Tolerance to Myelin Basic Protein in CD8-depleted Mice: Both CD4+ and CD8+ Cells Mediate Active Suppression. J Immunol. 1995 Jul 15;155(2):910-6. PubMed PMID: 7541826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression. AU - Chen,Y, AU - Inobe,J, AU - Weiner,H L, PY - 1995/7/15/pubmed PY - 1995/7/15/medline PY - 1995/7/15/entrez SP - 910 EP - 6 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 155 IS - 2 N2 - We have previously shown that orally administered myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis in both the Lewis rat and the SJL mouse. In the Lewis rat fed low doses of MBP, we found that protection can be adoptively transferred by CD8+ cells and that these cells inhibit immune responses via the secretion of TGF-beta after Ag-specific triggering. In the present study, we investigated the cellular requirements for the generation of active suppression following oral administration of MBP in SJL and (PLJ x SJL)F1 mice. We first determined the frequency of MBP cells secreting Th1 (IFN-gamma) and Th2 (IL-4/IL-10) cytokines or TGF-beta after oral administration of MBP. We found that in SJL mice, orally administered MBP (0.5 mg/feeding) led to an increased frequency of TGF-beta-, IL-4-, and IL-10-secreting cells and a decreased frequency of IFN-gamma-producing cells. This pattern was observed in both CD4+ and CD8+ populations; adoptive transfer of either CD4+ or CD8+ cells from orally tolerized mice suppressed autoimmune encephalomyelitis in recipient animals. We then studied the role of CD8+ cells on the generation of oral tolerance to MBP by depleting CD8+ cells in vivo with anti-CD8 mAb. Oral tolerance was successfully induced in such animals, as demonstrated by a decrease in clinical disease and T cell proliferative responses, although there was less TGF-beta production in vitro and less disease protection on days 20 to 22 in CD8-depleted animals. These studies demonstrate that CD4+ cells in the absence of CD8+ cells can mediate the active suppression component of oral tolerance in mice and that there is a reciprocal relationship between Th1- and Th2-type cytokine production associated with oral tolerization. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7541826/Induction_of_oral_tolerance_to_myelin_basic_protein_in_CD8_depleted_mice:_both_CD4+_and_CD8+_cells_mediate_active_suppression_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=7541826 DB - PRIME DP - Unbound Medicine ER -