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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
A model for sensory adaptation in naive CD4 T cells, illustrating the possible relationship between TCR engagement, CD5 expression, and responsiveness to TCR ligation. According to this model, naive CD4 T cells that interact more strongly than others with self-pMHC express higher levels of CD5. Their responsiveness to subsequent TCR ligation is dampened. The boundaries of the model remain to be defined. To the left, persistent lack of pMHC interactions may result in the loss of the cell from the naive peripheral T cell pool. To the right, excessive chronic stimulation may be accompanied by the loss of the naive T cell phenotype (reference 52).
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fig8: A model for sensory adaptation in naive CD4 T cells, illustrating the possible relationship between TCR engagement, CD5 expression, and responsiveness to TCR ligation. According to this model, naive CD4 T cells that interact more strongly than others with self-pMHC express higher levels of CD5. Their responsiveness to subsequent TCR ligation is dampened. The boundaries of the model remain to be defined. To the left, persistent lack of pMHC interactions may result in the loss of the cell from the naive peripheral T cell pool. To the right, excessive chronic stimulation may be accompanied by the loss of the naive T cell phenotype (reference 52).

Mentions: The data presented here show that CD5 levels on naive peripheral CD4 T cells are maintained by an active process which requires the availability of pMHC ligands on the part of the environment and the continued expression of p56lck on the part of the T cell. Reduced CD5 levels are predictive of elevated Ca2+ responses to TCR engagement in TCR transgenic CD4 T cells experimentally deprived of MHC contact as well as in unmanipulated polyclonal naive CD4 T cell populations. Despite this elevated responsiveness to TCR engagement by the surrogate ligand anti-CD3, naive polyclonal CD5low CD4 T cells proliferate poorly when their interaction with self-pMHC is tested by transfer into sublethally irradiated syngeneic hosts. As homeostatic proliferation in this experimental setting is promoted by pMHC recognition (30–32, 35) and we have shown that naive CD4 T cells reduce CD5 expression when experimentally deprived of MHC contact, the data are consistent with a model where CD5 levels reflect productive interactions with self-pMHC. Within a polyclonal repertoire, some naive CD4 T cells will engage self pMHC ligands more avidly than others. According to the model presented in Fig. 8 , the former become (or remain) CD5high and display dampened Ca2+ responses to anti-CD3 while the latter become (or remain) CD5low and display elevated Ca2+ responses.


Sensory adaptation in naive peripheral CD4 T cells.

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

A model for sensory adaptation in naive CD4 T cells, illustrating the possible relationship between TCR engagement, CD5 expression, and responsiveness to TCR ligation. According to this model, naive CD4 T cells that interact more strongly than others with self-pMHC express higher levels of CD5. Their responsiveness to subsequent TCR ligation is dampened. The boundaries of the model remain to be defined. To the left, persistent lack of pMHC interactions may result in the loss of the cell from the naive peripheral T cell pool. To the right, excessive chronic stimulation may be accompanied by the loss of the naive T cell phenotype (reference 52).
© Copyright Policy
Related In: Results  -  Collection

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

fig8: A model for sensory adaptation in naive CD4 T cells, illustrating the possible relationship between TCR engagement, CD5 expression, and responsiveness to TCR ligation. According to this model, naive CD4 T cells that interact more strongly than others with self-pMHC express higher levels of CD5. Their responsiveness to subsequent TCR ligation is dampened. The boundaries of the model remain to be defined. To the left, persistent lack of pMHC interactions may result in the loss of the cell from the naive peripheral T cell pool. To the right, excessive chronic stimulation may be accompanied by the loss of the naive T cell phenotype (reference 52).
Mentions: The data presented here show that CD5 levels on naive peripheral CD4 T cells are maintained by an active process which requires the availability of pMHC ligands on the part of the environment and the continued expression of p56lck on the part of the T cell. Reduced CD5 levels are predictive of elevated Ca2+ responses to TCR engagement in TCR transgenic CD4 T cells experimentally deprived of MHC contact as well as in unmanipulated polyclonal naive CD4 T cell populations. Despite this elevated responsiveness to TCR engagement by the surrogate ligand anti-CD3, naive polyclonal CD5low CD4 T cells proliferate poorly when their interaction with self-pMHC is tested by transfer into sublethally irradiated syngeneic hosts. As homeostatic proliferation in this experimental setting is promoted by pMHC recognition (30–32, 35) and we have shown that naive CD4 T cells reduce CD5 expression when experimentally deprived of MHC contact, the data are consistent with a model where CD5 levels reflect productive interactions with self-pMHC. Within a polyclonal repertoire, some naive CD4 T cells will engage self pMHC ligands more avidly than others. According to the model presented in Fig. 8 , the former become (or remain) CD5high and display dampened Ca2+ responses to anti-CD3 while the latter become (or remain) CD5low and display elevated Ca2+ responses.

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