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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

Identification of polymorphisms of TLR2 between SJL and B6 strains and expression of TLR2 on immune cells.A) Comparison of the sequence of TLR2 of SJL and B6. The non-synonymous and synonymous polymorphisms are boxed. Base (first line) and aminoacid (second line) sequences of B6 and the corresponding sequences (third and fourth lines, respectively) of SJL around the polymorphic residues are reported. B) Identification of enriched activated T cells, naïve T cells and APC in LN cells by scattering properties. SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb.. 8 days later, mice were sacrificed and cells from draining LN were loaded with CFSE and stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 monoclonal antibody. The colours define cells examined for TLR2 expression in panel C. C) SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb. Eight d later, mice were sacrificed and cells from draining LN were stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 mAb and with FITC labeled anti-TLR2 mAb. Expression of TLR2 was evaluated on high scattering CD3+ cells (activated T cells, red line), low scattering CD3+ cells (naïve T cells, shaded area) and CD3− cells (mostly APC, black line), as shown in B.
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pone-0055819-g003: Identification of polymorphisms of TLR2 between SJL and B6 strains and expression of TLR2 on immune cells.A) Comparison of the sequence of TLR2 of SJL and B6. The non-synonymous and synonymous polymorphisms are boxed. Base (first line) and aminoacid (second line) sequences of B6 and the corresponding sequences (third and fourth lines, respectively) of SJL around the polymorphic residues are reported. B) Identification of enriched activated T cells, naïve T cells and APC in LN cells by scattering properties. SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb.. 8 days later, mice were sacrificed and cells from draining LN were loaded with CFSE and stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 monoclonal antibody. The colours define cells examined for TLR2 expression in panel C. C) SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb. Eight d later, mice were sacrificed and cells from draining LN were stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 mAb and with FITC labeled anti-TLR2 mAb. Expression of TLR2 was evaluated on high scattering CD3+ cells (activated T cells, red line), low scattering CD3+ cells (naïve T cells, shaded area) and CD3− cells (mostly APC, black line), as shown in B.

Mentions: We sequenced the cDNA encoding for TLR2 from mice of SJL and B6 strains bred in our facility, as described in the Materials and Methods. The TLR2 sequence of B6 mice used in this study is the same as the one deposited at the NCBI (http://www.ncbi.nlm.nih.gov, accession numbers AK005043.1 for mRNA and BAB23770.1 for a sequence). The sequence obtained from the SJL mice displays 3 synonymous polymorphisms and one non-synonymous polymorphism, 83Met (B6) to Ile (SJL), in the second LRR (Fig. 3A).


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)

Identification of polymorphisms of TLR2 between SJL and B6 strains and expression of TLR2 on immune cells.A) Comparison of the sequence of TLR2 of SJL and B6. The non-synonymous and synonymous polymorphisms are boxed. Base (first line) and aminoacid (second line) sequences of B6 and the corresponding sequences (third and fourth lines, respectively) of SJL around the polymorphic residues are reported. B) Identification of enriched activated T cells, naïve T cells and APC in LN cells by scattering properties. SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb.. 8 days later, mice were sacrificed and cells from draining LN were loaded with CFSE and stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 monoclonal antibody. The colours define cells examined for TLR2 expression in panel C. C) SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb. Eight d later, mice were sacrificed and cells from draining LN were stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 mAb and with FITC labeled anti-TLR2 mAb. Expression of TLR2 was evaluated on high scattering CD3+ cells (activated T cells, red line), low scattering CD3+ cells (naïve T cells, shaded area) and CD3− cells (mostly APC, black line), as shown in B.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569447&req=5

pone-0055819-g003: Identification of polymorphisms of TLR2 between SJL and B6 strains and expression of TLR2 on immune cells.A) Comparison of the sequence of TLR2 of SJL and B6. The non-synonymous and synonymous polymorphisms are boxed. Base (first line) and aminoacid (second line) sequences of B6 and the corresponding sequences (third and fourth lines, respectively) of SJL around the polymorphic residues are reported. B) Identification of enriched activated T cells, naïve T cells and APC in LN cells by scattering properties. SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb.. 8 days later, mice were sacrificed and cells from draining LN were loaded with CFSE and stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 monoclonal antibody. The colours define cells examined for TLR2 expression in panel C. C) SJL, B6wt, F1 (SJLxB6wt) and F1 (SJLxB6tlr2−) mice were immunized with IFA containing 50 microgrammes/mouse of M tb. Eight d later, mice were sacrificed and cells from draining LN were stimulated with PPD. After 3 days, cells were collected and stained with PE-labeled anti-CD3 mAb and with FITC labeled anti-TLR2 mAb. Expression of TLR2 was evaluated on high scattering CD3+ cells (activated T cells, red line), low scattering CD3+ cells (naïve T cells, shaded area) and CD3− cells (mostly APC, black line), as shown in B.
Mentions: We sequenced the cDNA encoding for TLR2 from mice of SJL and B6 strains bred in our facility, as described in the Materials and Methods. The TLR2 sequence of B6 mice used in this study is the same as the one deposited at the NCBI (http://www.ncbi.nlm.nih.gov, accession numbers AK005043.1 for mRNA and BAB23770.1 for a sequence). The sequence obtained from the SJL mice displays 3 synonymous polymorphisms and one non-synonymous polymorphism, 83Met (B6) to Ile (SJL), in the second LRR (Fig. 3A).

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