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Impact of the TCR signal on regulatory T cell homeostasis, function, and trafficking.

Kim JK, Klinger M, Benjamin J, Xiao Y, Erle DJ, Littman DR, Killeen N - PLoS ONE (2009)

Bottom Line: Using an Ox40-cre allele that is prominently expressed in Treg cells, and a conditional allele of the gene encoding p56(Lck), we have examined the importance of TCR signaling in Treg cells.Inactivation of p56(Lck) resulted in abnormal Treg homeostasis characterized by impaired turnover, preferential redistribution to the lymph nodes, loss of suppressive function, and striking changes in gene expression.Abnormal Treg cell homeostasis and function did not reflect the involvement of p56(Lck) in CD4 function because these effects were not observed when CD4 expression was inactivated by Ox40-cre.The results make clear multiple aspects of Treg cell homeostasis and phenotype that are dependent on a sustained capacity to signal through the TCR.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.

ABSTRACT
Signaling through the T cell antigen receptor (TCR) is important for the homeostasis of naïve and memory CD4(+) T cells. The significance of TCR signaling in regulatory T (Treg) cells has not been systematically addressed. Using an Ox40-cre allele that is prominently expressed in Treg cells, and a conditional allele of the gene encoding p56(Lck), we have examined the importance of TCR signaling in Treg cells. Inactivation of p56(Lck) resulted in abnormal Treg homeostasis characterized by impaired turnover, preferential redistribution to the lymph nodes, loss of suppressive function, and striking changes in gene expression. Abnormal Treg cell homeostasis and function did not reflect the involvement of p56(Lck) in CD4 function because these effects were not observed when CD4 expression was inactivated by Ox40-cre.The results make clear multiple aspects of Treg cell homeostasis and phenotype that are dependent on a sustained capacity to signal through the TCR.

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p56Lck-deficient regulatory T cells.A. Flow cytometry data showing frequencies of Treg cells in mice of the indicated genotypes in the thymus, spleen and lymph nodes. B. Frequencies of thymic and peripheral Treg cells in individual mice of the indicated genotypes (bottom panel). The top panel shows total cell recovery from each of the tissues in the same mice. Asterisks identify differences (compared to control) that were statistically significant by ANOVA (p<0.05).
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pone-0006580-g003: p56Lck-deficient regulatory T cells.A. Flow cytometry data showing frequencies of Treg cells in mice of the indicated genotypes in the thymus, spleen and lymph nodes. B. Frequencies of thymic and peripheral Treg cells in individual mice of the indicated genotypes (bottom panel). The top panel shows total cell recovery from each of the tissues in the same mice. Asterisks identify differences (compared to control) that were statistically significant by ANOVA (p<0.05).

Mentions: Regulatory T cells were about two-fold reduced in number in the thymuses and spleens of Lck and Lck/Fyn mice compared to control or Fyn mice (Figure 3AB). By contrast their numbers were increased in the lymph nodes of the two Lck mutants (Figure 3B) but this was associated with little, if any, change in their representation as a fraction of the CD4+ population (Figure 3A). Instead, the apparent accumulation of p56Lck-deficient Treg cells in the lymph nodes was a consequence of mild lymphadenopathy in the mutant mice and an associated increase in T cell numbers (Figure 3B).


Impact of the TCR signal on regulatory T cell homeostasis, function, and trafficking.

Kim JK, Klinger M, Benjamin J, Xiao Y, Erle DJ, Littman DR, Killeen N - PLoS ONE (2009)

p56Lck-deficient regulatory T cells.A. Flow cytometry data showing frequencies of Treg cells in mice of the indicated genotypes in the thymus, spleen and lymph nodes. B. Frequencies of thymic and peripheral Treg cells in individual mice of the indicated genotypes (bottom panel). The top panel shows total cell recovery from each of the tissues in the same mice. Asterisks identify differences (compared to control) that were statistically significant by ANOVA (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2719063&req=5

pone-0006580-g003: p56Lck-deficient regulatory T cells.A. Flow cytometry data showing frequencies of Treg cells in mice of the indicated genotypes in the thymus, spleen and lymph nodes. B. Frequencies of thymic and peripheral Treg cells in individual mice of the indicated genotypes (bottom panel). The top panel shows total cell recovery from each of the tissues in the same mice. Asterisks identify differences (compared to control) that were statistically significant by ANOVA (p<0.05).
Mentions: Regulatory T cells were about two-fold reduced in number in the thymuses and spleens of Lck and Lck/Fyn mice compared to control or Fyn mice (Figure 3AB). By contrast their numbers were increased in the lymph nodes of the two Lck mutants (Figure 3B) but this was associated with little, if any, change in their representation as a fraction of the CD4+ population (Figure 3A). Instead, the apparent accumulation of p56Lck-deficient Treg cells in the lymph nodes was a consequence of mild lymphadenopathy in the mutant mice and an associated increase in T cell numbers (Figure 3B).

Bottom Line: Using an Ox40-cre allele that is prominently expressed in Treg cells, and a conditional allele of the gene encoding p56(Lck), we have examined the importance of TCR signaling in Treg cells.Inactivation of p56(Lck) resulted in abnormal Treg homeostasis characterized by impaired turnover, preferential redistribution to the lymph nodes, loss of suppressive function, and striking changes in gene expression.Abnormal Treg cell homeostasis and function did not reflect the involvement of p56(Lck) in CD4 function because these effects were not observed when CD4 expression was inactivated by Ox40-cre.The results make clear multiple aspects of Treg cell homeostasis and phenotype that are dependent on a sustained capacity to signal through the TCR.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.

ABSTRACT
Signaling through the T cell antigen receptor (TCR) is important for the homeostasis of naïve and memory CD4(+) T cells. The significance of TCR signaling in regulatory T (Treg) cells has not been systematically addressed. Using an Ox40-cre allele that is prominently expressed in Treg cells, and a conditional allele of the gene encoding p56(Lck), we have examined the importance of TCR signaling in Treg cells. Inactivation of p56(Lck) resulted in abnormal Treg homeostasis characterized by impaired turnover, preferential redistribution to the lymph nodes, loss of suppressive function, and striking changes in gene expression. Abnormal Treg cell homeostasis and function did not reflect the involvement of p56(Lck) in CD4 function because these effects were not observed when CD4 expression was inactivated by Ox40-cre.The results make clear multiple aspects of Treg cell homeostasis and phenotype that are dependent on a sustained capacity to signal through the TCR.

Show MeSH