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M tuberculosis in the adjuvant modulates time of appearance of CNS-specific effector T cells in the spleen through a polymorphic site of TLR2.

Nicolò C, Di Sante G, Procoli A, Migliara G, Piermattei A, Valentini M, Delogu G, Cittadini A, Constantin G, Ria F - PLoS ONE (2013)

Bottom Line: DC deliver information regulating trafficking of effector T cells along T-cell priming.Egress of T lymphocytes is regulated by TLR2 expressed on T cells.Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand.

View Article: PubMed Central - PubMed

Affiliation: Institute of General Pathology, Università Cattolica del S. Cuore, Rome, Italy.

ABSTRACT
DC deliver information regulating trafficking of effector T cells along T-cell priming. However, the role of pathogen-derived motives in the regulation of movement of T cells has not been studied. We hereinafter report that amount of M tuberculosis in the adjuvant modulates relocation of PLP139-151 specific T cells. In the presence of a low dose of M tuberculosis in the adjuvant, T cells (detected by CDR3 BV-BJ spectratyping, the so-called "immunoscope") mostly reach the spleen by day 28 after immunization ("late relocation") in the SJL strain, whereas T cells reach the spleen by d 14 with a high dose of M tuberculosis ("early relocation"). The C57Bl/6 background confers a dominant "early relocation" phenotype to F1 (SJL×C57Bl/6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 is responsible for "early/late" relocation phenotype. Egress of T lymphocytes is regulated by TLR2 expressed on T cells. Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand.

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Related in: MedlinePlus

Mobilization of T cells depends on the polymorphism of TLR2.Upper section: transfer of TLR2 of SJL onto B6 background. SJL mice (homozygous for TLR2 of SJL, ts+/+) mice were crossed with B6tlr2− (t-). F1 mice (genotype ts/t-) were then backcrossed with B6tlr2− and F2 mice of genotype ts/t- are further backcrossed with B6tlr2− generating F3 mice ts/t- that share ≈90% of their genome with B6wt. These latter mice (B6ts/t−) were crossed with SJL mice to generate TLR2-heterozygous F1 (SJLtsxB6t−) and TLR2-homozygous F1 (SJLtsxB6ts) mice. Lower section: these two groups of littermates were immunized with p139 in regular CFA and 14 days later the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was examined by immunoscope, as described above. Ten mice per group were examined, and mice of each group derived from two distinct (B6ts/t−×SJL) couples. Data are reported as RSI for the peak corresponding to the public TCR-beta chain for each individual mouse. The cut off value for the RSI at 1.7 is indicated.
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pone-0055819-g004: Mobilization of T cells depends on the polymorphism of TLR2.Upper section: transfer of TLR2 of SJL onto B6 background. SJL mice (homozygous for TLR2 of SJL, ts+/+) mice were crossed with B6tlr2− (t-). F1 mice (genotype ts/t-) were then backcrossed with B6tlr2− and F2 mice of genotype ts/t- are further backcrossed with B6tlr2− generating F3 mice ts/t- that share ≈90% of their genome with B6wt. These latter mice (B6ts/t−) were crossed with SJL mice to generate TLR2-heterozygous F1 (SJLtsxB6t−) and TLR2-homozygous F1 (SJLtsxB6ts) mice. Lower section: these two groups of littermates were immunized with p139 in regular CFA and 14 days later the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was examined by immunoscope, as described above. Ten mice per group were examined, and mice of each group derived from two distinct (B6ts/t−×SJL) couples. Data are reported as RSI for the peak corresponding to the public TCR-beta chain for each individual mouse. The cut off value for the RSI at 1.7 is indicated.

Mentions: In order to formally establish if the difference in sequence of TLR2 regulates the mobilization of T cells in response to regular CFA, we produced F1 mice having two copies of the TLR2 gene of SJL origin (F1 (SJLts×B6ts)). The procedure is shown in Fig. 4. “B6ts/t−” mice (i.e. mice of B6 background heterozygous for TLR2 of SJL (ts) and B6tlr2− (t-) origin) were bred with SJL mice, producing two types of F1 littermates, (SJL×B6tlr2−) and (SJL×B6ts), the former having one copy and the latter two copies of TLR2 of SJL origin. Results show that F1 mice (differing in gene load of TLR2 of SJL origin) display the same phenotype, and only 20% of the mice display a presence of these cells in the spleen in both groups, in contrast to 50% of the mice showing it in the LN. Thus, residue at position 83 (Met to Ile) of TLR2 is critical to determine “late” versus “early” appearance phenotype, while its gene load does not have a role.


M tuberculosis in the adjuvant modulates time of appearance of CNS-specific effector T cells in the spleen through a polymorphic site of TLR2.

Nicolò C, Di Sante G, Procoli A, Migliara G, Piermattei A, Valentini M, Delogu G, Cittadini A, Constantin G, Ria F - PLoS ONE (2013)

Mobilization of T cells depends on the polymorphism of TLR2.Upper section: transfer of TLR2 of SJL onto B6 background. SJL mice (homozygous for TLR2 of SJL, ts+/+) mice were crossed with B6tlr2− (t-). F1 mice (genotype ts/t-) were then backcrossed with B6tlr2− and F2 mice of genotype ts/t- are further backcrossed with B6tlr2− generating F3 mice ts/t- that share ≈90% of their genome with B6wt. These latter mice (B6ts/t−) were crossed with SJL mice to generate TLR2-heterozygous F1 (SJLtsxB6t−) and TLR2-homozygous F1 (SJLtsxB6ts) mice. Lower section: these two groups of littermates were immunized with p139 in regular CFA and 14 days later the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was examined by immunoscope, as described above. Ten mice per group were examined, and mice of each group derived from two distinct (B6ts/t−×SJL) couples. Data are reported as RSI for the peak corresponding to the public TCR-beta chain for each individual mouse. The cut off value for the RSI at 1.7 is indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569447&req=5

pone-0055819-g004: Mobilization of T cells depends on the polymorphism of TLR2.Upper section: transfer of TLR2 of SJL onto B6 background. SJL mice (homozygous for TLR2 of SJL, ts+/+) mice were crossed with B6tlr2− (t-). F1 mice (genotype ts/t-) were then backcrossed with B6tlr2− and F2 mice of genotype ts/t- are further backcrossed with B6tlr2− generating F3 mice ts/t- that share ≈90% of their genome with B6wt. These latter mice (B6ts/t−) were crossed with SJL mice to generate TLR2-heterozygous F1 (SJLtsxB6t−) and TLR2-homozygous F1 (SJLtsxB6ts) mice. Lower section: these two groups of littermates were immunized with p139 in regular CFA and 14 days later the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was examined by immunoscope, as described above. Ten mice per group were examined, and mice of each group derived from two distinct (B6ts/t−×SJL) couples. Data are reported as RSI for the peak corresponding to the public TCR-beta chain for each individual mouse. The cut off value for the RSI at 1.7 is indicated.
Mentions: In order to formally establish if the difference in sequence of TLR2 regulates the mobilization of T cells in response to regular CFA, we produced F1 mice having two copies of the TLR2 gene of SJL origin (F1 (SJLts×B6ts)). The procedure is shown in Fig. 4. “B6ts/t−” mice (i.e. mice of B6 background heterozygous for TLR2 of SJL (ts) and B6tlr2− (t-) origin) were bred with SJL mice, producing two types of F1 littermates, (SJL×B6tlr2−) and (SJL×B6ts), the former having one copy and the latter two copies of TLR2 of SJL origin. Results show that F1 mice (differing in gene load of TLR2 of SJL origin) display the same phenotype, and only 20% of the mice display a presence of these cells in the spleen in both groups, in contrast to 50% of the mice showing it in the LN. Thus, residue at position 83 (Met to Ile) of TLR2 is critical to determine “late” versus “early” appearance phenotype, while its gene load does not have a role.

Bottom Line: DC deliver information regulating trafficking of effector T cells along T-cell priming.Egress of T lymphocytes is regulated by TLR2 expressed on T cells.Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand.

View Article: PubMed Central - PubMed

Affiliation: Institute of General Pathology, Università Cattolica del S. Cuore, Rome, Italy.

ABSTRACT
DC deliver information regulating trafficking of effector T cells along T-cell priming. However, the role of pathogen-derived motives in the regulation of movement of T cells has not been studied. We hereinafter report that amount of M tuberculosis in the adjuvant modulates relocation of PLP139-151 specific T cells. In the presence of a low dose of M tuberculosis in the adjuvant, T cells (detected by CDR3 BV-BJ spectratyping, the so-called "immunoscope") mostly reach the spleen by day 28 after immunization ("late relocation") in the SJL strain, whereas T cells reach the spleen by d 14 with a high dose of M tuberculosis ("early relocation"). The C57Bl/6 background confers a dominant "early relocation" phenotype to F1 (SJL×C57Bl/6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 is responsible for "early/late" relocation phenotype. Egress of T lymphocytes is regulated by TLR2 expressed on T cells. Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand.

Show MeSH
Related in: MedlinePlus