CD8 Inhibits Signal Transduction through the T Cell Receptor in CD4-CD8- Thymocytes from T Cell Receptor Transgenic Mice Reconstituted with a Transgenic CD8α Molecule

Nicolai S C Van Oers, Soo Jeet Teh, Alex M. Garvin, Katherine A. Forbush, Roger M. Perlmutter, Hung Sia Teh

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

T cell repertoire selection processes involve intracellular signaling events generated through the TCR. The CD4 and CD8 coreceptor molecules can act as positive regulators of TCR signal transduction during these developmental processes. In this report, we have used TCR transgenic mice to determine whether TCR signaling can be modulated by the CD8 coreceptor molecule. These mice express on the majority of their T cells a TCR specific for the male (H-Y) Ag presented by the H-2Db MHC class I molecule. We show that CD4-CD8-, but not CD4-CD8+, thymocytes expressing the H-Y TCR responded with high intracellular calcium fluxes to TCR/CD3 stimulation without extensive receptor cross-linking. To examine the effects of CD8 expression on intracellular signaling responses in the CD4-CD8- cells, the H-Y TCR transgenic mice were mated with transgenic mice that constitutively expressed the CD8α molecule on all T cells. The expression of the CD8αα homodimer in the CD4-CD8- thymocytes led to impaired intracellular calcium responses and less efficient protein tyrosine phosphorylation of substrates after TCR engagement. In male H-2b H-Y transgenic mice, the majority of thymocytes have been deleted with the surviving cells expressing a high density of the transgenic TCR and exhibiting either a CD4-CD8- or CD4-CD8lo phenotype. It has been postulated that these cells escaped deletion by down-regulating the CD8 molecule. In the H-Y TCR/CD8α double transgenic male mice, the CD4-CD8lo cells were completely eliminated as a result of CD8α expression. However, the CD4-CD8- T cells were not deleted despite normal levels of the CD8α transgene expression. These results suggest that the CD4-CD8- thymocytes may not be susceptible to the same deletional mechanisms as other thymocytes expressing TCR-αβ.

Original languageEnglish (US)
Pages (from-to)777-790
Number of pages14
JournalJournal of Immunology
Volume151
Issue number2
StatePublished - Jul 15 1993

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Thymocytes
T-Cell Antigen Receptor
Transgenic Mice
Signal Transduction
T-Lymphocytes
Calcium
Transgenes
Tyrosine
Phosphorylation
Phenotype
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

CD8 Inhibits Signal Transduction through the T Cell Receptor in CD4-CD8- Thymocytes from T Cell Receptor Transgenic Mice Reconstituted with a Transgenic CD8α Molecule. / Van Oers, Nicolai S C; Teh, Soo Jeet; Garvin, Alex M.; Forbush, Katherine A.; Perlmutter, Roger M.; Teh, Hung Sia.

In: Journal of Immunology, Vol. 151, No. 2, 15.07.1993, p. 777-790.

Research output: Contribution to journalArticle

Van Oers, Nicolai S C ; Teh, Soo Jeet ; Garvin, Alex M. ; Forbush, Katherine A. ; Perlmutter, Roger M. ; Teh, Hung Sia. / CD8 Inhibits Signal Transduction through the T Cell Receptor in CD4-CD8- Thymocytes from T Cell Receptor Transgenic Mice Reconstituted with a Transgenic CD8α Molecule. In: Journal of Immunology. 1993 ; Vol. 151, No. 2. pp. 777-790.
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abstract = "T cell repertoire selection processes involve intracellular signaling events generated through the TCR. The CD4 and CD8 coreceptor molecules can act as positive regulators of TCR signal transduction during these developmental processes. In this report, we have used TCR transgenic mice to determine whether TCR signaling can be modulated by the CD8 coreceptor molecule. These mice express on the majority of their T cells a TCR specific for the male (H-Y) Ag presented by the H-2Db MHC class I molecule. We show that CD4-CD8-, but not CD4-CD8+, thymocytes expressing the H-Y TCR responded with high intracellular calcium fluxes to TCR/CD3 stimulation without extensive receptor cross-linking. To examine the effects of CD8 expression on intracellular signaling responses in the CD4-CD8- cells, the H-Y TCR transgenic mice were mated with transgenic mice that constitutively expressed the CD8α molecule on all T cells. The expression of the CD8αα homodimer in the CD4-CD8- thymocytes led to impaired intracellular calcium responses and less efficient protein tyrosine phosphorylation of substrates after TCR engagement. In male H-2b H-Y transgenic mice, the majority of thymocytes have been deleted with the surviving cells expressing a high density of the transgenic TCR and exhibiting either a CD4-CD8- or CD4-CD8lo phenotype. It has been postulated that these cells escaped deletion by down-regulating the CD8 molecule. In the H-Y TCR/CD8α double transgenic male mice, the CD4-CD8lo cells were completely eliminated as a result of CD8α expression. However, the CD4-CD8- T cells were not deleted despite normal levels of the CD8α transgene expression. These results suggest that the CD4-CD8- thymocytes may not be susceptible to the same deletional mechanisms as other thymocytes expressing TCR-αβ.",
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