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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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Appearance of T cells in the spleen is regulated by TLR2 expressed on T cells.ADetection of p139-specific T cells in SJLBV10 mice. One SJLBV10 mouse (at the 6th backcross onto SJL background) was immunized s. c. with p139 in regular CFA, as described above. Ten days later LN cells were obtained, stained with CFSE and cultured in the presence or absence of p139. The number of BV10+, p139-specific T cells in the draining LN is measured as the number of CFSElow BV10+ cells in the ag-stimulated sample, minus the number of the same cells in the non-stimulated sample. B) T cells were enriched from the spleen of naïve F1 mice of (SJLBV10×B6wt) or (SJLBV10×B6tlr2−), and transferred i. p. into naïve F1 mice of (SJL×B6wt) or (SJL×B6tlr2−). A week later, recipient mice were immunized s. c. with p139 in regular CFA, and after, further 14 days, cells from LN and spleen were prepared, and the presence of BV10+, p139-specific T cells was measured as described in Fig. 4a. The 11 non-transferred mice were 6 F1 (SJL×B6wt) mice and 5 F1 (SJL×B6tlr2−) mice, all challenged with p139 in regular CFA. Data are expressed as the number of BV10+, CFSElow, p139-specific cells/104 BV10+ cells.
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pone-0055819-g005: Appearance of T cells in the spleen is regulated by TLR2 expressed on T cells.ADetection of p139-specific T cells in SJLBV10 mice. One SJLBV10 mouse (at the 6th backcross onto SJL background) was immunized s. c. with p139 in regular CFA, as described above. Ten days later LN cells were obtained, stained with CFSE and cultured in the presence or absence of p139. The number of BV10+, p139-specific T cells in the draining LN is measured as the number of CFSElow BV10+ cells in the ag-stimulated sample, minus the number of the same cells in the non-stimulated sample. B) T cells were enriched from the spleen of naïve F1 mice of (SJLBV10×B6wt) or (SJLBV10×B6tlr2−), and transferred i. p. into naïve F1 mice of (SJL×B6wt) or (SJL×B6tlr2−). A week later, recipient mice were immunized s. c. with p139 in regular CFA, and after, further 14 days, cells from LN and spleen were prepared, and the presence of BV10+, p139-specific T cells was measured as described in Fig. 4a. The 11 non-transferred mice were 6 F1 (SJL×B6wt) mice and 5 F1 (SJL×B6tlr2−) mice, all challenged with p139 in regular CFA. Data are expressed as the number of BV10+, CFSElow, p139-specific cells/104 BV10+ cells.

Mentions: In order to trace p139-specific T cells, we prepared a transgenic mouse expressing the shared beta chain BV10-CASS SGS NTEV-BJ1.1 on the SJL background (SJLBV10). To detect T cells expressing the transgenic beta chain with available anti-BV10 monoclonal antibodies, we used the BV10 chain of the TCR type 2 haplotype as a backbone. Transgenic T cells proliferating in response to p139 after immunization can be detected by flow cytometry as BV10+ CFSElow cells (Fig. 5A).


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)

Appearance of T cells in the spleen is regulated by TLR2 expressed on T cells.ADetection of p139-specific T cells in SJLBV10 mice. One SJLBV10 mouse (at the 6th backcross onto SJL background) was immunized s. c. with p139 in regular CFA, as described above. Ten days later LN cells were obtained, stained with CFSE and cultured in the presence or absence of p139. The number of BV10+, p139-specific T cells in the draining LN is measured as the number of CFSElow BV10+ cells in the ag-stimulated sample, minus the number of the same cells in the non-stimulated sample. B) T cells were enriched from the spleen of naïve F1 mice of (SJLBV10×B6wt) or (SJLBV10×B6tlr2−), and transferred i. p. into naïve F1 mice of (SJL×B6wt) or (SJL×B6tlr2−). A week later, recipient mice were immunized s. c. with p139 in regular CFA, and after, further 14 days, cells from LN and spleen were prepared, and the presence of BV10+, p139-specific T cells was measured as described in Fig. 4a. The 11 non-transferred mice were 6 F1 (SJL×B6wt) mice and 5 F1 (SJL×B6tlr2−) mice, all challenged with p139 in regular CFA. Data are expressed as the number of BV10+, CFSElow, p139-specific cells/104 BV10+ cells.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569447&req=5

pone-0055819-g005: Appearance of T cells in the spleen is regulated by TLR2 expressed on T cells.ADetection of p139-specific T cells in SJLBV10 mice. One SJLBV10 mouse (at the 6th backcross onto SJL background) was immunized s. c. with p139 in regular CFA, as described above. Ten days later LN cells were obtained, stained with CFSE and cultured in the presence or absence of p139. The number of BV10+, p139-specific T cells in the draining LN is measured as the number of CFSElow BV10+ cells in the ag-stimulated sample, minus the number of the same cells in the non-stimulated sample. B) T cells were enriched from the spleen of naïve F1 mice of (SJLBV10×B6wt) or (SJLBV10×B6tlr2−), and transferred i. p. into naïve F1 mice of (SJL×B6wt) or (SJL×B6tlr2−). A week later, recipient mice were immunized s. c. with p139 in regular CFA, and after, further 14 days, cells from LN and spleen were prepared, and the presence of BV10+, p139-specific T cells was measured as described in Fig. 4a. The 11 non-transferred mice were 6 F1 (SJL×B6wt) mice and 5 F1 (SJL×B6tlr2−) mice, all challenged with p139 in regular CFA. Data are expressed as the number of BV10+, CFSElow, p139-specific cells/104 BV10+ cells.
Mentions: In order to trace p139-specific T cells, we prepared a transgenic mouse expressing the shared beta chain BV10-CASS SGS NTEV-BJ1.1 on the SJL background (SJLBV10). To detect T cells expressing the transgenic beta chain with available anti-BV10 monoclonal antibodies, we used the BV10 chain of the TCR type 2 haplotype as a backbone. Transgenic T cells proliferating in response to p139 after immunization can be detected by flow cytometry as BV10+ CFSElow cells (Fig. 5A).

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