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Macrophages play an essential role in antigen-specific immune suppression mediated by T CD8⁺ cell-derived exosomes.
- Source :
-
Immunology [Immunology] 2015 Sep; Vol. 146 (1), pp. 23-32. Date of Electronic Publication: 2015 Apr 27. - Publication Year :
- 2015
-
Abstract
- Murine contact sensitivity (CS) reaction could be antigen-specifically regulated by T CD8(+) suppressor (Ts) lymphocytes releasing microRNA-150 in antibody light-chain-coated exosomes that were formerly suggested to suppress CS through action on macrophages (Mφ). The present studies investigated the role of Mφ in Ts cell-exosome-mediated antigen-specific suppression as well as modulation of Mφ antigen-presenting function in humoral and cellular immunity by suppressive exosomes. Mice depleted of Mφ by clodronate liposomes could not be tolerized and did not produce suppressive exosomes. Moreover, isolated T effector lymphocytes transferring CS were suppressed by exosomes only in the presence of Mφ, demonstrating the substantial role of Mφ in the generation and action of Ts cell regulatory exosomes. Further, significant decrease of number of splenic B cells producing trinitrophenyl (TNP) -specific antibodies with the alteration of the ratio of serum titres of IgM to IgG was observed in recipients of exosome-treated, antigen-pulsed Mφ and the significant suppression of CS was demonstrated in recipients of exosome-treated, TNP-conjugated Mφ. Additionally, exosome-pulsed, TNP-conjugated Mφ mediated suppression of CS in mice pre-treated with a low-dose of cyclophosphamide, suggesting de novo induction of T regulatory (Treg) lymphocytes. Treg cell involvement in the effector phase of the studied suppression mechanism was proved by unsuccessful tolerization of DEREG mice depleted of Treg lymphocytes. Furthermore, the inhibition of proliferation of CS effector cells cultured with exosome-treated Mφ in a transmembrane manner was observed. Our results demonstrated the essential role of Mφ in antigen-specific immune suppression mediated by Ts cell-derived exosomes and realized by induction of Treg lymphocytes and inhibition of T effector cell proliferation.<br /> (© 2015 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Cell Proliferation
Cells, Cultured
Cyclophosphamide pharmacology
Dermatitis, Contact immunology
Immunoglobulin G blood
Immunoglobulin G immunology
Immunoglobulin M blood
Immunoglobulin M immunology
Immunosuppression Therapy methods
Immunosuppressive Agents pharmacology
Lymphocyte Depletion
Mice
Mice, Inbred BALB C
Mice, Inbred CBA
MicroRNAs genetics
Trinitrobenzenes immunology
CD8-Positive T-Lymphocytes immunology
Exosomes immunology
Immune Tolerance immunology
Macrophages immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2567
- Volume :
- 146
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 25808106
- Full Text :
- https://doi.org/10.1111/imm.12466