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Sensory adaptation in naive peripheral CD4 T cells.

Smith K, Seddon B, Purbhoo MA, Zamoyska R, Fisher AG, Merkenschlager M - J. Exp. Med. (2001)

Bottom Line: Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck).Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen.Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

View Article: PubMed Central - PubMed

Affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, ICSM Hammersmith Hospital, London W12 0NN, UK.

ABSTRACT
T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck). Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

Show MeSH
Continued expression of lck is required for the maintenance of CD5 levels on naive peripheral CD4 T cells. CD5 expression by CD4 T cells from C57Bl/10 (wild-type), Lck1/rtTA-C/lckneg mice given doxycyclin, and Lck1/rtTA-C/lckneg mice taken off doxycyclin 12 wk earlier were analyzed by flow cytometry.
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fig3: Continued expression of lck is required for the maintenance of CD5 levels on naive peripheral CD4 T cells. CD5 expression by CD4 T cells from C57Bl/10 (wild-type), Lck1/rtTA-C/lckneg mice given doxycyclin, and Lck1/rtTA-C/lckneg mice taken off doxycyclin 12 wk earlier were analyzed by flow cytometry.

Mentions: To begin to elucidate the mechanisms that maintain CD5 in peripheral CD4 T cells we made use of a recently described mouse model, Lck1/rtTA-C/lckneg, that allows the regulated expression of p56lck by reconstituting lck-deficient mice with a p56lck transgene under the control of the tetracyclin response element responsive to the reverse tetracyclin transactivator (48). lck expression is controlled by administration of the tetracycline derivative doxycycline. In the presence of doxycycline, lck expression in Lck1/rtTA-C/lckneg mice is higher than wild-type in the thymus but lower in peripheral T cells. Withdrawal of the drug results in the loss of lck expression. The resulting lck-deficient T cells show impaired homeostatic proliferation but normal long-term survival and, surprisingly, normal levels of basal CD3 ζ phosphorylation (48). We asked whether loss of lck expression was accompanied by a decrease of CD5 levels on CD4 T cells and found a decrease to ∼50% of the levels in wild type mice, compared with ∼80% in doxycycline-fed mice (Fig. 3) . We conclude that, in contrast to basal ζ chain phosphorylation (48), the maintenance of CD5 levels on peripheral CD4 T cells requires the continued expression of lck.


Sensory adaptation in naive peripheral CD4 T cells.

Smith K, Seddon B, Purbhoo MA, Zamoyska R, Fisher AG, Merkenschlager M - J. Exp. Med. (2001)

Continued expression of lck is required for the maintenance of CD5 levels on naive peripheral CD4 T cells. CD5 expression by CD4 T cells from C57Bl/10 (wild-type), Lck1/rtTA-C/lckneg mice given doxycyclin, and Lck1/rtTA-C/lckneg mice taken off doxycyclin 12 wk earlier were analyzed by flow cytometry.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195983&req=5

fig3: Continued expression of lck is required for the maintenance of CD5 levels on naive peripheral CD4 T cells. CD5 expression by CD4 T cells from C57Bl/10 (wild-type), Lck1/rtTA-C/lckneg mice given doxycyclin, and Lck1/rtTA-C/lckneg mice taken off doxycyclin 12 wk earlier were analyzed by flow cytometry.
Mentions: To begin to elucidate the mechanisms that maintain CD5 in peripheral CD4 T cells we made use of a recently described mouse model, Lck1/rtTA-C/lckneg, that allows the regulated expression of p56lck by reconstituting lck-deficient mice with a p56lck transgene under the control of the tetracyclin response element responsive to the reverse tetracyclin transactivator (48). lck expression is controlled by administration of the tetracycline derivative doxycycline. In the presence of doxycycline, lck expression in Lck1/rtTA-C/lckneg mice is higher than wild-type in the thymus but lower in peripheral T cells. Withdrawal of the drug results in the loss of lck expression. The resulting lck-deficient T cells show impaired homeostatic proliferation but normal long-term survival and, surprisingly, normal levels of basal CD3 ζ phosphorylation (48). We asked whether loss of lck expression was accompanied by a decrease of CD5 levels on CD4 T cells and found a decrease to ∼50% of the levels in wild type mice, compared with ∼80% in doxycycline-fed mice (Fig. 3) . We conclude that, in contrast to basal ζ chain phosphorylation (48), the maintenance of CD5 levels on peripheral CD4 T cells requires the continued expression of lck.

Bottom Line: Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck).Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen.Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

View Article: PubMed Central - PubMed

Affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, ICSM Hammersmith Hospital, London W12 0NN, UK.

ABSTRACT
T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck). Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

Show MeSH