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Rapid depletion of peripheral antigen-specific T cells in TCR-transgenic mice after oral administration of myelin basic protein.
J Immunol. 2001 May 01; 166(9):5773-81.JI

Abstract

In myelin basic protein (MBP)-specific TCR-transgenic (Tg) mice, peripheral T cells express the Valpha2.3/Vbeta8.2-Tg TCR, demonstrate vigorous proliferative responses to MBP in vitro, and can exhibit experimental autoimmune encephalomyelitis (EAE) within 5 days of pertussis toxin injection. We explored the effects of oral administration of MBP on the cellular trafficking of the MBP-specific TCR-Tg cells and the ability of oral MBP to protect Tg mice from EAE. Tg mice were fed MBP, OVA or vehicle and sacrificed at various times after feeding. An immediate and dramatic decrease in Valpha2.3/Vbeta8.2(+)-Tg cells was observed in the periphery within 1 h after feeding. By 3 days after feeding, the percentage of Tg cells increased to near control levels, but decreased again by 10 days. When MBP or vehicle-fed Tg mice were challenged for EAE at this point, disease was severe in the vehicle-fed mice and reduced in the MBP-fed mice over the 40-day observation period. In vitro studies revealed a biphasic pattern of MBP proliferative unresponsiveness and an induction of Th1 cytokines. Immunohistochemical staining showed that the number of Tg cells found in the intestinal lamina propria increased dramatically as the number of Tg cells in the periphery decreased. There was no apparent proliferation of Tg cells in the lamina propria, indicating that Tg cells trafficked there from the periphery. Taken together, these results suggest that T cell trafficking into the site of Ag deposition acts to protect the TCR-Tg mouse from EAE.

Authors+Show Affiliations

Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

11313421

Citation

Meyer, A L., et al. "Rapid Depletion of Peripheral Antigen-specific T Cells in TCR-transgenic Mice After Oral Administration of Myelin Basic Protein." Journal of Immunology (Baltimore, Md. : 1950), vol. 166, no. 9, 2001, pp. 5773-81.
Meyer AL, Benson J, Song F, et al. Rapid depletion of peripheral antigen-specific T cells in TCR-transgenic mice after oral administration of myelin basic protein. J Immunol. 2001;166(9):5773-81.
Meyer, A. L., Benson, J., Song, F., Javed, N., Gienapp, I. E., Goverman, J., Brabb, T. A., Hood, L., & Whitacre, C. C. (2001). Rapid depletion of peripheral antigen-specific T cells in TCR-transgenic mice after oral administration of myelin basic protein. Journal of Immunology (Baltimore, Md. : 1950), 166(9), 5773-81.
Meyer AL, et al. Rapid Depletion of Peripheral Antigen-specific T Cells in TCR-transgenic Mice After Oral Administration of Myelin Basic Protein. J Immunol. 2001 May 1;166(9):5773-81. PubMed PMID: 11313421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid depletion of peripheral antigen-specific T cells in TCR-transgenic mice after oral administration of myelin basic protein. AU - Meyer,A L, AU - Benson,J, AU - Song,F, AU - Javed,N, AU - Gienapp,I E, AU - Goverman,J, AU - Brabb,T A, AU - Hood,L, AU - Whitacre,C C, PY - 2001/4/21/pubmed PY - 2001/7/20/medline PY - 2001/4/21/entrez SP - 5773 EP - 81 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 166 IS - 9 N2 - In myelin basic protein (MBP)-specific TCR-transgenic (Tg) mice, peripheral T cells express the Valpha2.3/Vbeta8.2-Tg TCR, demonstrate vigorous proliferative responses to MBP in vitro, and can exhibit experimental autoimmune encephalomyelitis (EAE) within 5 days of pertussis toxin injection. We explored the effects of oral administration of MBP on the cellular trafficking of the MBP-specific TCR-Tg cells and the ability of oral MBP to protect Tg mice from EAE. Tg mice were fed MBP, OVA or vehicle and sacrificed at various times after feeding. An immediate and dramatic decrease in Valpha2.3/Vbeta8.2(+)-Tg cells was observed in the periphery within 1 h after feeding. By 3 days after feeding, the percentage of Tg cells increased to near control levels, but decreased again by 10 days. When MBP or vehicle-fed Tg mice were challenged for EAE at this point, disease was severe in the vehicle-fed mice and reduced in the MBP-fed mice over the 40-day observation period. In vitro studies revealed a biphasic pattern of MBP proliferative unresponsiveness and an induction of Th1 cytokines. Immunohistochemical staining showed that the number of Tg cells found in the intestinal lamina propria increased dramatically as the number of Tg cells in the periphery decreased. There was no apparent proliferation of Tg cells in the lamina propria, indicating that Tg cells trafficked there from the periphery. Taken together, these results suggest that T cell trafficking into the site of Ag deposition acts to protect the TCR-Tg mouse from EAE. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11313421/Rapid_depletion_of_peripheral_antigen_specific_T_cells_in_TCR_transgenic_mice_after_oral_administration_of_myelin_basic_protein_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11313421 DB - PRIME DP - Unbound Medicine ER -