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Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats.
J Immunol. 1998 Jan 15; 160(2):700-7.JI

Abstract

Unselected CD4+8+ rat thymocytes, generated in vitro from their direct precursors, are readily converted to functional TCRhigh T cells by stimulation with immobilized TCR-specific mAb plus IL-2. Lineage decision invariably occurs toward CD4-8+, regardless of the timing of TCR stimulation after entry into the CD4+8+ compartment or the concentration of TCR-specific mAb used for stimulation. CD4-specific mAb synergizes with suboptimal TCR-specific mAb in inducing T cell maturation, but lineage decision remains exclusively CD4-8+. These results contrast with those obtained in mice, in which Abs to the TCR complex were shown to promote CD4+8- T cell maturation from CD4+8+ thymocytes. Surprisingly, when rat and mouse CD4+8+ thymocytes were stimulated with PMA/ionomycin under identical conditions, the opposite lineage commitment was observed, i.e., mouse thymocytes responded with the generation of CD4+8- and rat thymocytes with the generation of CD4-8+ cells. It thus seems that CD4+8+ thymocytes of the two species respond with opposite lineage decisions to strong activating signals such as given by TCR-specific mAb or PMA/ionomycin. A possible key to this difference lies in the availability of p56lck for coreceptor. supported signaling. We show that in contrast to mouse CD4+8+ thymocytes, which express both a complete and a truncated CD8 alpha-chain (CD8 alpha') unable to bind p56lck, rat thymocytes only express full-length CD8 alpha molecules. Mice, but not rats, therefore may use CD8 alpha' as a "dominant negative" coreceptor chain to attenuate the CD8 signal, thereby facilitating MHC class II recognition through the higher amount of p56lck delivered, and rats may use a different mechanism for MHC class distinction during positive selection.

Authors+Show Affiliations

Institute for Virology and Immunobiology, University of Würzburg, Germany.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

9551905

Citation

Mitnacht, R, et al. "Opposite CD4/CD8 Lineage Decisions of CD4+8+ Mouse and Rat Thymocytes to Equivalent Triggering Signals: Correlation With Thymic Expression of a Truncated CD8 Alpha Chain in Mice but Not Rats." Journal of Immunology (Baltimore, Md. : 1950), vol. 160, no. 2, 1998, pp. 700-7.
Mitnacht R, Bischof A, Torres-Nagel N, et al. Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats. J Immunol. 1998;160(2):700-7.
Mitnacht, R., Bischof, A., Torres-Nagel, N., & Hünig, T. (1998). Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats. Journal of Immunology (Baltimore, Md. : 1950), 160(2), 700-7.
Mitnacht R, et al. Opposite CD4/CD8 Lineage Decisions of CD4+8+ Mouse and Rat Thymocytes to Equivalent Triggering Signals: Correlation With Thymic Expression of a Truncated CD8 Alpha Chain in Mice but Not Rats. J Immunol. 1998 Jan 15;160(2):700-7. PubMed PMID: 9551905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats. AU - Mitnacht,R, AU - Bischof,A, AU - Torres-Nagel,N, AU - Hünig,T, PY - 1998/4/29/pubmed PY - 1998/4/29/medline PY - 1998/4/29/entrez SP - 700 EP - 7 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 160 IS - 2 N2 - Unselected CD4+8+ rat thymocytes, generated in vitro from their direct precursors, are readily converted to functional TCRhigh T cells by stimulation with immobilized TCR-specific mAb plus IL-2. Lineage decision invariably occurs toward CD4-8+, regardless of the timing of TCR stimulation after entry into the CD4+8+ compartment or the concentration of TCR-specific mAb used for stimulation. CD4-specific mAb synergizes with suboptimal TCR-specific mAb in inducing T cell maturation, but lineage decision remains exclusively CD4-8+. These results contrast with those obtained in mice, in which Abs to the TCR complex were shown to promote CD4+8- T cell maturation from CD4+8+ thymocytes. Surprisingly, when rat and mouse CD4+8+ thymocytes were stimulated with PMA/ionomycin under identical conditions, the opposite lineage commitment was observed, i.e., mouse thymocytes responded with the generation of CD4+8- and rat thymocytes with the generation of CD4-8+ cells. It thus seems that CD4+8+ thymocytes of the two species respond with opposite lineage decisions to strong activating signals such as given by TCR-specific mAb or PMA/ionomycin. A possible key to this difference lies in the availability of p56lck for coreceptor. supported signaling. We show that in contrast to mouse CD4+8+ thymocytes, which express both a complete and a truncated CD8 alpha-chain (CD8 alpha') unable to bind p56lck, rat thymocytes only express full-length CD8 alpha molecules. Mice, but not rats, therefore may use CD8 alpha' as a "dominant negative" coreceptor chain to attenuate the CD8 signal, thereby facilitating MHC class II recognition through the higher amount of p56lck delivered, and rats may use a different mechanism for MHC class distinction during positive selection. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9551905/Opposite_CD4/CD8_lineage_decisions_of_CD4+8+_mouse_and_rat_thymocytes_to_equivalent_triggering_signals:_correlation_with_thymic_expression_of_a_truncated_CD8_alpha_chain_in_mice_but_not_rats_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9551905 DB - PRIME DP - Unbound Medicine ER -