Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions

Douglas A. Carlow, Nicolai S C Van Oers, Soo Jeet Teh, Hung Sia Teh

Research output: Contribution to journalArticle

78 Citations (Scopus)

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-1α or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1β 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.

Original languageEnglish (US)
Pages (from-to)1595-1603
Number of pages9
JournalJournal of Immunology
Volume148
Issue number6
StatePublished - Mar 15 1992

Fingerprint

Lymphocyte Function-Associated Antigen-1
Thymocytes
Dendritic Cells
Antigens
Transgenic Mice
T-Lymphocytes
Intercellular Adhesion Molecule-1
B-Lymphocytes
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions. / Carlow, Douglas A.; Van Oers, Nicolai S C; Teh, Soo Jeet; Teh, Hung Sia.

In: Journal of Immunology, Vol. 148, No. 6, 15.03.1992, p. 1595-1603.

Research output: Contribution to journalArticle

Carlow, Douglas A. ; Van Oers, Nicolai S C ; Teh, Soo Jeet ; Teh, Hung Sia. / Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions. In: Journal of Immunology. 1992 ; Vol. 148, No. 6. pp. 1595-1603.
@article{6c063a9a9d5349d69b5fec6bb421a0fa,
title = "Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions",
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-1α or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1β 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.",
author = "Carlow, {Douglas A.} and {Van Oers}, {Nicolai S C} and Teh, {Soo Jeet} and Teh, {Hung Sia}",
year = "1992",
month = "3",
day = "15",
language = "English (US)",
volume = "148",
pages = "1595--1603",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions

AU - Carlow, Douglas A.

AU - Van Oers, Nicolai S C

AU - Teh, Soo Jeet

AU - Teh, Hung Sia

PY - 1992/3/15

Y1 - 1992/3/15

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-1α or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1β 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.

AB - 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-1α or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1β 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.

UR - http://www.scopus.com/inward/record.url?scp=0026574558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026574558&partnerID=8YFLogxK

M3 - Article

C2 - 1347300

AN - SCOPUS:0026574558

VL - 148

SP - 1595

EP - 1603

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -