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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

Amount of M tuberculosis in the adjuvant modulates appearance of p139-specific-T cells in the SJL strain.SJL mice were immunized with p139 in IFA containing or not 50 or 200 microgrammes/mouse of M tuberculosis (regular or enriched CFA, respectively). In all the figures, closed symbols refer to LN cells and open symbols to spleen cells. A) Time course of appearance of p139-specific BV10+ cells in LN and spleen following challenge with antigen in regular CFA. BV10+, p139-specific T cells were measured by immunoscope in draining LN and spleen. B) Presence of p139-specific BV10+ cells in the spleen at d 14 after s.c. immunization depends on the amount of M tuberculosis in the adjuvant. SJL mice were immunized s.c. with 100 microliters of a 1∶1 suspension of p139 in regular CFA (11 mice), in enriched CFA (6 mice) or in IFA alone (8 mice). Two weeks later, mice were sacrificed and LN and spleen were examined for the presence of p139-specific BV10+ cells by immunoscope. Data are reported as R.S.I., and each symbol represents LN or spleen of one mouse, and the dashed line represents the cut off value for positivity in SJL mice. c) The number of p139 specific T cells in the spleen 14 d after challenge with peptide in enriched CFA is inversely related to the number of the same cells in the LN. SJL mice were immunized s.c. with p139 in enriched CFA (4 mice). Two weeks later, cells from draining LN and spleen were stained with CFSE and cultured in the presence or absence of 10 microgrammes/ml of p139. After 3 days, cells were recovered and stained with PE-labelled anti CD4 monoclonal antibody. p139-specific cells are calculated as CFSElow CD4+ cells in the ag-stimulated sample minus the number of the same cells in the non-stimulated sample.
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pone-0055819-g001: Amount of M tuberculosis in the adjuvant modulates appearance of p139-specific-T cells in the SJL strain.SJL mice were immunized with p139 in IFA containing or not 50 or 200 microgrammes/mouse of M tuberculosis (regular or enriched CFA, respectively). In all the figures, closed symbols refer to LN cells and open symbols to spleen cells. A) Time course of appearance of p139-specific BV10+ cells in LN and spleen following challenge with antigen in regular CFA. BV10+, p139-specific T cells were measured by immunoscope in draining LN and spleen. B) Presence of p139-specific BV10+ cells in the spleen at d 14 after s.c. immunization depends on the amount of M tuberculosis in the adjuvant. SJL mice were immunized s.c. with 100 microliters of a 1∶1 suspension of p139 in regular CFA (11 mice), in enriched CFA (6 mice) or in IFA alone (8 mice). Two weeks later, mice were sacrificed and LN and spleen were examined for the presence of p139-specific BV10+ cells by immunoscope. Data are reported as R.S.I., and each symbol represents LN or spleen of one mouse, and the dashed line represents the cut off value for positivity in SJL mice. c) The number of p139 specific T cells in the spleen 14 d after challenge with peptide in enriched CFA is inversely related to the number of the same cells in the LN. SJL mice were immunized s.c. with p139 in enriched CFA (4 mice). Two weeks later, cells from draining LN and spleen were stained with CFSE and cultured in the presence or absence of 10 microgrammes/ml of p139. After 3 days, cells were recovered and stained with PE-labelled anti CD4 monoclonal antibody. p139-specific cells are calculated as CFSElow CD4+ cells in the ag-stimulated sample minus the number of the same cells in the non-stimulated sample.

Mentions: We immunized SJL mice with p139 in IFA containing 50 microgrammes/mouse of M tb (regular CFA), and monitored time of appearance of the shared BV10+ cells in draining LN and spleen by CDR3 BV-BJ spectratyping (the so-called “immunoscope”), mirroring the similar experiment performed after immunization of mice with the same amount of peptide but in enriched CFA [11]. Results are shown in Fig. 1A.


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)

Amount of M tuberculosis in the adjuvant modulates appearance of p139-specific-T cells in the SJL strain.SJL mice were immunized with p139 in IFA containing or not 50 or 200 microgrammes/mouse of M tuberculosis (regular or enriched CFA, respectively). In all the figures, closed symbols refer to LN cells and open symbols to spleen cells. A) Time course of appearance of p139-specific BV10+ cells in LN and spleen following challenge with antigen in regular CFA. BV10+, p139-specific T cells were measured by immunoscope in draining LN and spleen. B) Presence of p139-specific BV10+ cells in the spleen at d 14 after s.c. immunization depends on the amount of M tuberculosis in the adjuvant. SJL mice were immunized s.c. with 100 microliters of a 1∶1 suspension of p139 in regular CFA (11 mice), in enriched CFA (6 mice) or in IFA alone (8 mice). Two weeks later, mice were sacrificed and LN and spleen were examined for the presence of p139-specific BV10+ cells by immunoscope. Data are reported as R.S.I., and each symbol represents LN or spleen of one mouse, and the dashed line represents the cut off value for positivity in SJL mice. c) The number of p139 specific T cells in the spleen 14 d after challenge with peptide in enriched CFA is inversely related to the number of the same cells in the LN. SJL mice were immunized s.c. with p139 in enriched CFA (4 mice). Two weeks later, cells from draining LN and spleen were stained with CFSE and cultured in the presence or absence of 10 microgrammes/ml of p139. After 3 days, cells were recovered and stained with PE-labelled anti CD4 monoclonal antibody. p139-specific cells are calculated as CFSElow CD4+ cells in the ag-stimulated sample minus the number of the same cells in the non-stimulated sample.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569447&req=5

pone-0055819-g001: Amount of M tuberculosis in the adjuvant modulates appearance of p139-specific-T cells in the SJL strain.SJL mice were immunized with p139 in IFA containing or not 50 or 200 microgrammes/mouse of M tuberculosis (regular or enriched CFA, respectively). In all the figures, closed symbols refer to LN cells and open symbols to spleen cells. A) Time course of appearance of p139-specific BV10+ cells in LN and spleen following challenge with antigen in regular CFA. BV10+, p139-specific T cells were measured by immunoscope in draining LN and spleen. B) Presence of p139-specific BV10+ cells in the spleen at d 14 after s.c. immunization depends on the amount of M tuberculosis in the adjuvant. SJL mice were immunized s.c. with 100 microliters of a 1∶1 suspension of p139 in regular CFA (11 mice), in enriched CFA (6 mice) or in IFA alone (8 mice). Two weeks later, mice were sacrificed and LN and spleen were examined for the presence of p139-specific BV10+ cells by immunoscope. Data are reported as R.S.I., and each symbol represents LN or spleen of one mouse, and the dashed line represents the cut off value for positivity in SJL mice. c) The number of p139 specific T cells in the spleen 14 d after challenge with peptide in enriched CFA is inversely related to the number of the same cells in the LN. SJL mice were immunized s.c. with p139 in enriched CFA (4 mice). Two weeks later, cells from draining LN and spleen were stained with CFSE and cultured in the presence or absence of 10 microgrammes/ml of p139. After 3 days, cells were recovered and stained with PE-labelled anti CD4 monoclonal antibody. p139-specific cells are calculated as CFSElow CD4+ cells in the ag-stimulated sample minus the number of the same cells in the non-stimulated sample.
Mentions: We immunized SJL mice with p139 in IFA containing 50 microgrammes/mouse of M tb (regular CFA), and monitored time of appearance of the shared BV10+ cells in draining LN and spleen by CDR3 BV-BJ spectratyping (the so-called “immunoscope”), mirroring the similar experiment performed after immunization of mice with the same amount of peptide but in enriched CFA [11]. Results are shown in Fig. 1A.

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