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Evidence for Immune Responses to a Self-Antigen in Lung Transplantation: Role of Type V Collagen-Specific T Cells in the Pathogenesis of Lung Allograft Rejection
- Source :
- The Journal of Immunology. 169:1542-1549
- Publication Year :
- 2002
- Publisher :
- The American Association of Immunologists, 2002.
-
Abstract
- We have reported that lung allograft rejection involves an immune response to a native protein in the lung, type V collagen (col(V)), and that col(V)-induced oral tolerance prevented acute and chronic rejection. In support of these findings col(V) fragments were detected in allografts during rejection, but not in normal lungs. The purpose of the current study was to isolate and characterize col(V)-specific allograft-infiltrating T cells and to determine their contribution to the rejection response in vivo. Two col(V)-specific T cell lines, LT1 and LT3, were isolated from F344 (RT1lv1) rat lung allografts during rejection that occurred after transplantation into WKY (RT1l) recipients. Both cell lines, but not normal lung lymphocytes, proliferated in response to col(V). Neither LT1 nor LT3 proliferated in response to alloantigens. LT1 and LT3 were CD4+CD25− and produced IFN-γ in response to col(V). Compared with normal CD4+ T cells, both cell lines expressed a limited V-β TCR repertoire. Each cell strongly expressed V-β 9 and 16, but differed in expression of other V-βs. Adoptive transfer of each cell line did not induce pathology in lungs of normal WKY rats. In contrast, adoptive transfer of LT1, but not LT3, caused marked peribronchiolar and perivascular inflammation in isograft (WKY) lungs and abrogated col(V)-induced oral tolerance to allograft (F344) lungs. Collectively, these data show that lung allograft rejection involves both allo- and autoimmune responses, and graft destruction that occurs during the rejection response may expose allograft-infiltrating T cells to potentially antigenic epitopes in col(V).
- Subjects :
- Graft Rejection
Male
Isoantigens
Adoptive cell transfer
Receptors, Antigen, T-Cell, alpha-beta
T-Lymphocytes
medicine.medical_treatment
T cell
Isograft
Immunology
Autoimmunity
Biology
Autoantigens
Rats, Inbred WKY
Cell Line
Immune system
Antigen
medicine
Animals
Transplantation, Homologous
Immunology and Allergy
Lung transplantation
Hypersensitivity, Delayed
IL-2 receptor
respiratory system
Rats, Inbred F344
Rats
Transplantation
surgical procedures, operative
medicine.anatomical_structure
Matrix Metalloproteinase 9
Collagen Type V
Lung Transplantation
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 169
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....46f87a799031609d5d959030bd3ba079