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B7/CTLA4 pathway is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice.
- Source :
-
Transplantation [Transplantation] 2002 Sep 15; Vol. 74 (5), pp. 732-8. - Publication Year :
- 2002
-
Abstract
- Background: The mechanism of hyporesponsiveness induced by intratracheal (IT) delivery of alloantigen was examined and its effect on cardiac graft survival was assessed in studies in mice.<br />Methods: In CBA (H2 ) mice, donor splenocytes were given by IT delivery 7 days before transplantation of a C57BL/10 (H2 ) heart. To determine whether regulatory cells were involved in hyporesponsiveness, splenocytes from mice given IT delivery of alloantigen and antibodies for B7-1, B7-2, or CTLA4 were adoptively transferred to naïve secondary recipients 7 days after delivery; those recipients underwent heart transplantation the same day. Effects on cell proliferation and cytokine production of splenocytes from mice given IT delivery of alloantigen were examined in mixed leukocyte cultures (MLC).<br />Results: Cardiac graft survival was significantly prolonged in mice given IT delivery of alloantigen (median survival time [MST], 81 days); those given syngeneic splenocytes rejected grafts acutely (MST, 7 days; P<0.05). Adoptive transfer of splenocytes also significantly prolonged survival of cardiac grafts in secondary recipients (MST, 62 days). When B7-1, B7-2, or CTLA4 antibody was combined with IT delivery of alloantigen in the first recipient, all grafts were rejected within 14 days in second recipients after adoptive transfer. In mixed leukocyte cultures, splenocytes from these mice did not respond to alloantigen and production of interleukin-4 and interleukin-10 was increased.<br />Conclusions: Donor splenocytes delivered IT induced hyporesponsiveness and regulatory cells in our animal model, and such induction was dependent on B7-1, B7-2, and CTLA4 signals.
- Subjects :
- Abatacept
Administration, Oral
Animals
Antigens, CD
CTLA-4 Antigen
Immunosuppression Therapy methods
Isoantigens administration & dosage
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Spleen immunology
Time Factors
Adoptive Transfer
Antigens, Differentiation immunology
B7-1 Antigen immunology
Graft Survival immunology
Heart Transplantation immunology
Immunoconjugates
Immunoglobulin Fc Fragments immunology
Isoantigens immunology
Lymphocyte Transfusion methods
Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 74
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 12352894
- Full Text :
- https://doi.org/10.1097/00007890-200209150-00024