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Effects of immunosuppressants on induction of regulatory cells after intratracheal delivery of alloantigen.
- Source :
-
Transplantation [Transplantation] 2005 Apr 27; Vol. 79 (8), pp. 904-13. - Publication Year :
- 2005
-
Abstract
- Background: We previously reported that intratracheal delivery (ITD) of alloantigen generated regulatory cells in mice. Here, we examined the effect of various doses of conventional immunosuppressants (FK506, cyclosporine A, azathioprine, mycophenolate mofetil, and rapamycin) on inducing regulatory cells in our model.<br />Methods: CBA mice (primary recipients) were given C57BL/6 splenocytes by ITD and either no additional treatment or various doses of an immunosuppressant. Seven days later, splenocytes from these mice were adoptively transferred into naive secondary CBA recipients that underwent C57BL/6 cardiac grafting the same day.<br />Results: Adoptive transfer from primary recipients given ITD of splenocytes alone induced prolonged allograft survival in secondary recipients (median survival time [MST], 50 days), suggesting that regulatory cells were generated. When ITD of alloantigen was combined with daily administration of 0.1 mg/kg FK506 or 0.2 mg/kg rapamycin, graft survival was similarly prolonged (MST 55 and 50 days, respectively). When combined with 20 or 40 mg/kg MMF or 0.4 mg/kg rapamycin, the majority of recipients demonstrated indefinite survival (MST, >100 days in all groups). When ITD of alloantigen was combined with 0.3, 0.5, or 1.0 mg/kg FK506; 5, 10, or 25 mg/kg cyclosporine A; or 1.0 or 2.0 mg/kg azathioprine, allografts were rejected acutely (MST 7-13 days).<br />Conclusion: Generation of regulatory cells by ITD of alloantigen was facilitated by mycophenolate mofetil and high doses of rapamycin but abrogated by cyclosporine A, azathioprine, and high doses of FK506. Low doses of rapamycin and of FK506 did not interfere with generation of regulatory cells.
- Subjects :
- Adoptive Transfer
Animals
Azathioprine pharmacology
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
Cyclosporine pharmacology
Dendritic Cells immunology
Graft Survival immunology
Interleukin-2 biosynthesis
Interleukin-2 metabolism
Mice
Mycophenolic Acid pharmacology
Sirolimus pharmacology
Spleen cytology
Spleen metabolism
Tacrolimus pharmacology
Time Factors
Tissue Donors
Transplantation
Immunosuppression Therapy
Immunosuppressive Agents pharmacology
Isoantigens administration & dosage
Isoantigens immunology
Mycophenolic Acid analogs & derivatives
Spleen drug effects
Spleen immunology
Trachea immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 79
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 15849542
- Full Text :
- https://doi.org/10.1097/01.tp.0000158023.21233.de