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Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions.
J Immunol. 1992 Mar 15; 148(6):1595-603.JI

Abstract

An in vitro assay was used for assessing the participation of various cell surface molecules and the efficacy of various cell types in the deletion of Ag-specific immature thymocytes. Thymocytes from mice expressing a transgenic TCR specific for the male Ag presented by the H-2Db class I MHC molecule were used as a target for deletion. In H-2d transgenic mice, cells bearing the transgenic TCR are not subjected to thymic selection as a consequence of the absence of the restricting H-2Db molecule but, nevertheless, express this TCR on the vast majority of immature CD4+8+ thymocytes. In this report we show that CD4+8+ thymocytes from H-2d TCR-transgenic mice are preferentially killed upon in vitro culture with male APC; DC were particularly effective in mediating in vitro deletion when compared with either B cells or T cells. Deletion of CD4+8+ thymocytes by DC was H-2b restricted and could be inhibited by mAb to either LFA-1 alpha or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1 beta were without effect. These results are the first direct evidence of LFA-1 involvement in negative selection and provide further direct support for the participation of CD8/class I MHC interactions in this process. Like the requirements for deletion, activation of mature male-specific CD4-8+ T cells from female H-2b TCR-transgenic mice was also largely dependent on Ag presentation by DC and required both LFA-1/ICAM and CD8/class I MHC interactions; these results support the view that activation and deletion may represent maturation stage-dependent consequences of T cells encountering the same APC. Finally, our results also support the hypothesis that negative selection (deletion) does not require previous positive selection because deletion was observed under conditions where positive selection had not occurred.

Authors+Show Affiliations

Department of Microbiology, University of British Columbia, Vancouver, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1347300

Citation

Carlow, D A., et al. "Deletion of Antigen-specific Immature Thymocytes By Dendritic Cells Requires LFA-1/ICAM Interactions." Journal of Immunology (Baltimore, Md. : 1950), vol. 148, no. 6, 1992, pp. 1595-603.
Carlow DA, van Oers NS, Teh SJ, et al. Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions. J Immunol. 1992;148(6):1595-603.
Carlow, D. A., van Oers, N. S., Teh, S. J., & Teh, H. S. (1992). Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions. Journal of Immunology (Baltimore, Md. : 1950), 148(6), 1595-603.
Carlow DA, et al. Deletion of Antigen-specific Immature Thymocytes By Dendritic Cells Requires LFA-1/ICAM Interactions. J Immunol. 1992 Mar 15;148(6):1595-603. PubMed PMID: 1347300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions. AU - Carlow,D A, AU - van Oers,N S, AU - Teh,S J, AU - Teh,H S, PY - 1992/3/15/pubmed PY - 1992/3/15/medline PY - 1992/3/15/entrez SP - 1595 EP - 603 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 148 IS - 6 N2 - An in vitro assay was used for assessing the participation of various cell surface molecules and the efficacy of various cell types in the deletion of Ag-specific immature thymocytes. Thymocytes from mice expressing a transgenic TCR specific for the male Ag presented by the H-2Db class I MHC molecule were used as a target for deletion. In H-2d transgenic mice, cells bearing the transgenic TCR are not subjected to thymic selection as a consequence of the absence of the restricting H-2Db molecule but, nevertheless, express this TCR on the vast majority of immature CD4+8+ thymocytes. In this report we show that CD4+8+ thymocytes from H-2d TCR-transgenic mice are preferentially killed upon in vitro culture with male APC; DC were particularly effective in mediating in vitro deletion when compared with either B cells or T cells. Deletion of CD4+8+ thymocytes by DC was H-2b restricted and could be inhibited by mAb to either LFA-1 alpha or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1 beta were without effect. These results are the first direct evidence of LFA-1 involvement in negative selection and provide further direct support for the participation of CD8/class I MHC interactions in this process. Like the requirements for deletion, activation of mature male-specific CD4-8+ T cells from female H-2b TCR-transgenic mice was also largely dependent on Ag presentation by DC and required both LFA-1/ICAM and CD8/class I MHC interactions; these results support the view that activation and deletion may represent maturation stage-dependent consequences of T cells encountering the same APC. Finally, our results also support the hypothesis that negative selection (deletion) does not require previous positive selection because deletion was observed under conditions where positive selection had not occurred. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1347300/Deletion_of_antigen_specific_immature_thymocytes_by_dendritic_cells_requires_LFA_1/ICAM_interactions_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=1347300 DB - PRIME DP - Unbound Medicine ER -