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In vivo instruction of suppressor commitment in naive T cells.

Apostolou I, von Boehmer H - J. Exp. Med. (2004)

Bottom Line: The induction of antigen-specific tolerance in the mature immune system of the intact organism has met with limited success.Therefore, nonspecific immunosuppression has been the treatment of choice to prevent unwanted immunity.The described procedure resembles approaches of tolerance induction used decades ago, induces tolerance in the absence of immunity, and holds the promise to become an effective means of inducing antigen-specific tolerance prospectively, whereas its power to suppress already ongoing immune responses remains to be determined.

View Article: PubMed Central - PubMed

Affiliation: Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, MA 02115, USA.

ABSTRACT
The induction of antigen-specific tolerance in the mature immune system of the intact organism has met with limited success. Therefore, nonspecific immunosuppression has been the treatment of choice to prevent unwanted immunity. Here, it is shown that prolonged subcutaneous infusion of low doses of peptide by means of osmotic pumps transforms mature T cells into CD4+25+ suppressor cells that can persist for long periods of time in the absence of antigen and confer specific immunologic tolerance upon challenge with antigen. The described procedure resembles approaches of tolerance induction used decades ago, induces tolerance in the absence of immunity, and holds the promise to become an effective means of inducing antigen-specific tolerance prospectively, whereas its power to suppress already ongoing immune responses remains to be determined.

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Related in: MedlinePlus

Ag-specific tolerance in peptide-infused nontransgenic BALB/c mice. Control BALB/c mice and HA peptide-infused BALB/c mice were immunized into the footpad with HA protein in IFA. Draining LN cells of the latter mice as well as popliteal LN cells of unmanipulated BALB/c mice were stimulated in vitro with either the whole HA protein or the infused HA peptide. Data are mean ± SD from triplicate wells and are representative of at least two independent experiments.
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fig5: Ag-specific tolerance in peptide-infused nontransgenic BALB/c mice. Control BALB/c mice and HA peptide-infused BALB/c mice were immunized into the footpad with HA protein in IFA. Draining LN cells of the latter mice as well as popliteal LN cells of unmanipulated BALB/c mice were stimulated in vitro with either the whole HA protein or the infused HA peptide. Data are mean ± SD from triplicate wells and are representative of at least two independent experiments.

Mentions: It was important to test whether tolerance could not only be induced in cells expressing transgenic TCRs but also in nonmanipulated CD4+ cells by the described protocol. Therefore, BALB/c mice or HA peptide-infused BALB/c mice (15 d after pump implant) were immunized into each footpad with 1 μg of highly immunogenic HA protein in IFA. 13 d after immunization, draining LN cells as well as mesenteric LN cells were collected and restimulated in vitro with either the entire HA protein or the HA peptide. Draining LN cells of immunized control mice proliferated vigorously to both protein and peptide stimuli (Fig. 5), whereas mesenteric LN cells from immunized mice and LN cells of nonimmunized BALB/c mice did not (not depicted). HA peptide infusion of animals before immunization resulted in the complete suppression of the in vitro recall response of draining LN cells to both in vitro stimuli (Fig. 5). Thus, the described peptide infusion is suited to induce tolerance to the entire protein from which the peptide is derived in normal mice.


In vivo instruction of suppressor commitment in naive T cells.

Apostolou I, von Boehmer H - J. Exp. Med. (2004)

Ag-specific tolerance in peptide-infused nontransgenic BALB/c mice. Control BALB/c mice and HA peptide-infused BALB/c mice were immunized into the footpad with HA protein in IFA. Draining LN cells of the latter mice as well as popliteal LN cells of unmanipulated BALB/c mice were stimulated in vitro with either the whole HA protein or the infused HA peptide. Data are mean ± SD from triplicate wells and are representative of at least two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211808&req=5

fig5: Ag-specific tolerance in peptide-infused nontransgenic BALB/c mice. Control BALB/c mice and HA peptide-infused BALB/c mice were immunized into the footpad with HA protein in IFA. Draining LN cells of the latter mice as well as popliteal LN cells of unmanipulated BALB/c mice were stimulated in vitro with either the whole HA protein or the infused HA peptide. Data are mean ± SD from triplicate wells and are representative of at least two independent experiments.
Mentions: It was important to test whether tolerance could not only be induced in cells expressing transgenic TCRs but also in nonmanipulated CD4+ cells by the described protocol. Therefore, BALB/c mice or HA peptide-infused BALB/c mice (15 d after pump implant) were immunized into each footpad with 1 μg of highly immunogenic HA protein in IFA. 13 d after immunization, draining LN cells as well as mesenteric LN cells were collected and restimulated in vitro with either the entire HA protein or the HA peptide. Draining LN cells of immunized control mice proliferated vigorously to both protein and peptide stimuli (Fig. 5), whereas mesenteric LN cells from immunized mice and LN cells of nonimmunized BALB/c mice did not (not depicted). HA peptide infusion of animals before immunization resulted in the complete suppression of the in vitro recall response of draining LN cells to both in vitro stimuli (Fig. 5). Thus, the described peptide infusion is suited to induce tolerance to the entire protein from which the peptide is derived in normal mice.

Bottom Line: The induction of antigen-specific tolerance in the mature immune system of the intact organism has met with limited success.Therefore, nonspecific immunosuppression has been the treatment of choice to prevent unwanted immunity.The described procedure resembles approaches of tolerance induction used decades ago, induces tolerance in the absence of immunity, and holds the promise to become an effective means of inducing antigen-specific tolerance prospectively, whereas its power to suppress already ongoing immune responses remains to be determined.

View Article: PubMed Central - PubMed

Affiliation: Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, MA 02115, USA.

ABSTRACT
The induction of antigen-specific tolerance in the mature immune system of the intact organism has met with limited success. Therefore, nonspecific immunosuppression has been the treatment of choice to prevent unwanted immunity. Here, it is shown that prolonged subcutaneous infusion of low doses of peptide by means of osmotic pumps transforms mature T cells into CD4+25+ suppressor cells that can persist for long periods of time in the absence of antigen and confer specific immunologic tolerance upon challenge with antigen. The described procedure resembles approaches of tolerance induction used decades ago, induces tolerance in the absence of immunity, and holds the promise to become an effective means of inducing antigen-specific tolerance prospectively, whereas its power to suppress already ongoing immune responses remains to be determined.

Show MeSH
Related in: MedlinePlus