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

M. Azizul Haque, Teruaki Mizobuchi, Kazuhiro Yasufuku, Takehiko Fujisawa, Randy Brutkiewicz, Yan Zheng, Kena Woods, Gerald N. Smith, Oscar Cummings, Kathleen M. Heidler, Janice Blum, David S. Wilkes

Research output: Contribution to journalArticle

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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 (RT11v1) rat lung allografts during rejection that occurred after transplantation into WKY (RT11) 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).

Original languageEnglish
Pages (from-to)1542-1549
Number of pages8
JournalJournal of Immunology
Volume169
Issue number3
StatePublished - Aug 1 2002

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Collagen Type V
Lung Transplantation
Autoantigens
Allografts
T-Lymphocytes
Lung
Cell Line
Adoptive Transfer
Isografts
Transplantation Tolerance
Isoantigens
Inbred WKY Rats
Inbred F344 Rats
Autoimmunity
Epitopes
Transplantation
Lymphocytes
Pathology
Inflammation
Transplants

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Haque, M. Azizul; Mizobuchi, Teruaki; Yasufuku, Kazuhiro; Fujisawa, Takehiko; Brutkiewicz, Randy; Zheng, Yan; Woods, Kena; Smith, Gerald N.; Cummings, Oscar; Heidler, Kathleen M.; Blum, Janice; Wilkes, David S.

In: Journal of Immunology, Vol. 169, No. 3, 01.08.2002, p. 1542-1549.

Research output: Contribution to journalArticle

Haque, MA, Mizobuchi, T, Yasufuku, K, Fujisawa, T, Brutkiewicz, R, Zheng, Y, Woods, K, Smith, GN, Cummings, O, Heidler, KM, Blum, J & Wilkes, DS 2002, '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', Journal of Immunology, vol. 169, no. 3, pp. 1542-1549.
Haque, M. Azizul ; Mizobuchi, Teruaki ; Yasufuku, Kazuhiro ; Fujisawa, Takehiko ; Brutkiewicz, Randy ; Zheng, Yan ; Woods, Kena ; Smith, Gerald N. ; Cummings, Oscar ; Heidler, Kathleen M. ; Blum, Janice ; Wilkes, David S. / 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. In: Journal of Immunology. 2002 ; Vol. 169, No. 3. pp. 1542-1549.
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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 (RT11v1) rat lung allografts during rejection that occurred after transplantation into WKY (RT11) 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).",
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AU - Yasufuku, Kazuhiro

AU - Fujisawa, Takehiko

AU - Brutkiewicz, Randy

AU - Zheng, Yan

AU - Woods, Kena

AU - Smith, Gerald N.

AU - Cummings, Oscar

AU - Heidler, Kathleen M.

AU - Blum, Janice

AU - Wilkes, David S.

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