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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 is strain and TLR2-dependent. F1 (SJLxB6wt), F1 (SJLxB6tlr−) (A, C) or SJL (B, D) mice were immunized with p139 in IFA in the presence of the indicated amounts of killed M tb (A), or of PPD (B, C) or of a 1∶1 w/w mixture of PAM2-(CSK)3 and PAM3-(CSK)3 (D). The number of mice for each group is indicated in the figure. Fourteen days later mice were sacrificed and the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was measured by immunoscope. Data are reported as RSI for the peak corresponding to the public BV10 TCR-beta chain for each individual mouse. Dashed lines indicate the cut off value for positivity (established as described in Results). E: 4 F1 (SJLxB6wt, circles) mice and 5 F1 (SJLxB6tlr2−, triangles) mice were immunized with regular CFA in PBS. Two weeks later cells from draining LN (full symbols) and spleen (open symbols) were recovered, labeled with CFSE and cultured in the presence or absence (background) of PPD. After 3 days, the number of CD3+ cells that had specifically divided in response to PPD was determined as % of CFSElow CD3+ cells over total CD3+ cells in the PPD stimulated sample minus % of CFSElow CD3+ cells over total CD3+ cells in background sample.
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pone-0055819-g002: Mobilization of T cells is strain and TLR2-dependent. F1 (SJLxB6wt), F1 (SJLxB6tlr−) (A, C) or SJL (B, D) mice were immunized with p139 in IFA in the presence of the indicated amounts of killed M tb (A), or of PPD (B, C) or of a 1∶1 w/w mixture of PAM2-(CSK)3 and PAM3-(CSK)3 (D). The number of mice for each group is indicated in the figure. Fourteen days later mice were sacrificed and the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was measured by immunoscope. Data are reported as RSI for the peak corresponding to the public BV10 TCR-beta chain for each individual mouse. Dashed lines indicate the cut off value for positivity (established as described in Results). E: 4 F1 (SJLxB6wt, circles) mice and 5 F1 (SJLxB6tlr2−, triangles) mice were immunized with regular CFA in PBS. Two weeks later cells from draining LN (full symbols) and spleen (open symbols) were recovered, labeled with CFSE and cultured in the presence or absence (background) of PPD. After 3 days, the number of CD3+ cells that had specifically divided in response to PPD was determined as % of CFSElow CD3+ cells over total CD3+ cells in the PPD stimulated sample minus % of CFSElow CD3+ cells over total CD3+ cells in background sample.

Mentions: Seven F1 (SJLxB6wt) mice were immunized s. c. with p139 in regular CFA, in two experiments. Two weeks later, we found that BV10+ cells were detected in the spleen at the same frequency of draining LN (3/7, Fig. 2A, left column), although we had used regular CFA as adjuvant.


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 is strain and TLR2-dependent. F1 (SJLxB6wt), F1 (SJLxB6tlr−) (A, C) or SJL (B, D) mice were immunized with p139 in IFA in the presence of the indicated amounts of killed M tb (A), or of PPD (B, C) or of a 1∶1 w/w mixture of PAM2-(CSK)3 and PAM3-(CSK)3 (D). The number of mice for each group is indicated in the figure. Fourteen days later mice were sacrificed and the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was measured by immunoscope. Data are reported as RSI for the peak corresponding to the public BV10 TCR-beta chain for each individual mouse. Dashed lines indicate the cut off value for positivity (established as described in Results). E: 4 F1 (SJLxB6wt, circles) mice and 5 F1 (SJLxB6tlr2−, triangles) mice were immunized with regular CFA in PBS. Two weeks later cells from draining LN (full symbols) and spleen (open symbols) were recovered, labeled with CFSE and cultured in the presence or absence (background) of PPD. After 3 days, the number of CD3+ cells that had specifically divided in response to PPD was determined as % of CFSElow CD3+ cells over total CD3+ cells in the PPD stimulated sample minus % of CFSElow CD3+ cells over total CD3+ cells in background sample.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569447&req=5

pone-0055819-g002: Mobilization of T cells is strain and TLR2-dependent. F1 (SJLxB6wt), F1 (SJLxB6tlr−) (A, C) or SJL (B, D) mice were immunized with p139 in IFA in the presence of the indicated amounts of killed M tb (A), or of PPD (B, C) or of a 1∶1 w/w mixture of PAM2-(CSK)3 and PAM3-(CSK)3 (D). The number of mice for each group is indicated in the figure. Fourteen days later mice were sacrificed and the presence of T cells carrying the public TCR-beta chain in LN (closed symbols) and spleen (open symbols) was measured by immunoscope. Data are reported as RSI for the peak corresponding to the public BV10 TCR-beta chain for each individual mouse. Dashed lines indicate the cut off value for positivity (established as described in Results). E: 4 F1 (SJLxB6wt, circles) mice and 5 F1 (SJLxB6tlr2−, triangles) mice were immunized with regular CFA in PBS. Two weeks later cells from draining LN (full symbols) and spleen (open symbols) were recovered, labeled with CFSE and cultured in the presence or absence (background) of PPD. After 3 days, the number of CD3+ cells that had specifically divided in response to PPD was determined as % of CFSElow CD3+ cells over total CD3+ cells in the PPD stimulated sample minus % of CFSElow CD3+ cells over total CD3+ cells in background sample.
Mentions: Seven F1 (SJLxB6wt) mice were immunized s. c. with p139 in regular CFA, in two experiments. Two weeks later, we found that BV10+ cells were detected in the spleen at the same frequency of draining LN (3/7, Fig. 2A, left column), although we had used regular CFA as adjuvant.

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