Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells

Diana Zelenika, Elizabeth Adams, Andrew Mellor, Elizabeth Simpson, Phillip Chandler, Brigitte Stockinger, Herman Waldmann, Stephen P. Cobbold

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

We wished to determine whether CD4+ T cells could reject a skin graft that was discordant for a single minor transplantation Ag in the absence of CD8+ T cells or Ab. Transgenic A1(M) mice were constructed that express the rearranged Vβ8.2 and Vα10 TCR genes from a T cell clone that is specific for the male Ag (H-Y) in the context of H2-Eκ. In addition, the RAG-1(-/-) background was bred onto these mice to eliminate any endogenous TCR rearrangements. As expected, clonal deletion was found to be complete in the thymus of male A1(M)xRAG-1(-/-) mice, while only CD4+ T cells were positively selected and found in the periphery of females. Female A1(M)xRAG- 1(-/-) mice were able to rapidly reject (in <14 days) male (but not female) skin grafts in a CD4-dependent fashion. After multiple grafts, it was confirmed that no CD8+ T cells or surface Ig+ B cells were present. An immunofluorescent analysis of spleen cells after grafting showed that the majority of T cells expressed activation markers (CD44, CD25, and intracytoplasmic IL-2) and a significant proportion were making IFN-γ and IL-4. Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin.

Original languageEnglish (US)
Pages (from-to)1868-1874
Number of pages7
JournalJournal of Immunology
Volume161
Issue number4
StatePublished - Aug 15 1998

Fingerprint

Th2 Cells
Th1 Cells
B-Lymphocytes
T-Lymphocytes
Transplants
Skin
Clonal Deletion
Interleukin-4
Thymus Gland
Interleukin-2
Spleen
Clone Cells
Transplantation
Cell Line

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Zelenika, D., Adams, E., Mellor, A., Simpson, E., Chandler, P., Stockinger, B., ... Cobbold, S. P. (1998). Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells. Journal of Immunology, 161(4), 1868-1874.

Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells : No requirement for CD8+ T cells or B cells. / Zelenika, Diana; Adams, Elizabeth; Mellor, Andrew; Simpson, Elizabeth; Chandler, Phillip; Stockinger, Brigitte; Waldmann, Herman; Cobbold, Stephen P.

In: Journal of Immunology, Vol. 161, No. 4, 15.08.1998, p. 1868-1874.

Research output: Contribution to journalArticle

Zelenika, D, Adams, E, Mellor, A, Simpson, E, Chandler, P, Stockinger, B, Waldmann, H & Cobbold, SP 1998, 'Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells', Journal of Immunology, vol. 161, no. 4, pp. 1868-1874.
Zelenika D, Adams E, Mellor A, Simpson E, Chandler P, Stockinger B et al. Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells. Journal of Immunology. 1998 Aug 15;161(4):1868-1874.
Zelenika, Diana ; Adams, Elizabeth ; Mellor, Andrew ; Simpson, Elizabeth ; Chandler, Phillip ; Stockinger, Brigitte ; Waldmann, Herman ; Cobbold, Stephen P. / Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells : No requirement for CD8+ T cells or B cells. In: Journal of Immunology. 1998 ; Vol. 161, No. 4. pp. 1868-1874.
@article{6d4058e7b15c49a28292d03079467ec6,
title = "Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells",
abstract = "We wished to determine whether CD4+ T cells could reject a skin graft that was discordant for a single minor transplantation Ag in the absence of CD8+ T cells or Ab. Transgenic A1(M) mice were constructed that express the rearranged Vβ8.2 and Vα10 TCR genes from a T cell clone that is specific for the male Ag (H-Y) in the context of H2-Eκ. In addition, the RAG-1(-/-) background was bred onto these mice to eliminate any endogenous TCR rearrangements. As expected, clonal deletion was found to be complete in the thymus of male A1(M)xRAG-1(-/-) mice, while only CD4+ T cells were positively selected and found in the periphery of females. Female A1(M)xRAG- 1(-/-) mice were able to rapidly reject (in <14 days) male (but not female) skin grafts in a CD4-dependent fashion. After multiple grafts, it was confirmed that no CD8+ T cells or surface Ig+ B cells were present. An immunofluorescent analysis of spleen cells after grafting showed that the majority of T cells expressed activation markers (CD44, CD25, and intracytoplasmic IL-2) and a significant proportion were making IFN-γ and IL-4. Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin.",
author = "Diana Zelenika and Elizabeth Adams and Andrew Mellor and Elizabeth Simpson and Phillip Chandler and Brigitte Stockinger and Herman Waldmann and Cobbold, {Stephen P.}",
year = "1998",
month = "8",
day = "15",
language = "English (US)",
volume = "161",
pages = "1868--1874",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells

T2 - No requirement for CD8+ T cells or B cells

AU - Zelenika, Diana

AU - Adams, Elizabeth

AU - Mellor, Andrew

AU - Simpson, Elizabeth

AU - Chandler, Phillip

AU - Stockinger, Brigitte

AU - Waldmann, Herman

AU - Cobbold, Stephen P.

PY - 1998/8/15

Y1 - 1998/8/15

N2 - We wished to determine whether CD4+ T cells could reject a skin graft that was discordant for a single minor transplantation Ag in the absence of CD8+ T cells or Ab. Transgenic A1(M) mice were constructed that express the rearranged Vβ8.2 and Vα10 TCR genes from a T cell clone that is specific for the male Ag (H-Y) in the context of H2-Eκ. In addition, the RAG-1(-/-) background was bred onto these mice to eliminate any endogenous TCR rearrangements. As expected, clonal deletion was found to be complete in the thymus of male A1(M)xRAG-1(-/-) mice, while only CD4+ T cells were positively selected and found in the periphery of females. Female A1(M)xRAG- 1(-/-) mice were able to rapidly reject (in <14 days) male (but not female) skin grafts in a CD4-dependent fashion. After multiple grafts, it was confirmed that no CD8+ T cells or surface Ig+ B cells were present. An immunofluorescent analysis of spleen cells after grafting showed that the majority of T cells expressed activation markers (CD44, CD25, and intracytoplasmic IL-2) and a significant proportion were making IFN-γ and IL-4. Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin.

AB - We wished to determine whether CD4+ T cells could reject a skin graft that was discordant for a single minor transplantation Ag in the absence of CD8+ T cells or Ab. Transgenic A1(M) mice were constructed that express the rearranged Vβ8.2 and Vα10 TCR genes from a T cell clone that is specific for the male Ag (H-Y) in the context of H2-Eκ. In addition, the RAG-1(-/-) background was bred onto these mice to eliminate any endogenous TCR rearrangements. As expected, clonal deletion was found to be complete in the thymus of male A1(M)xRAG-1(-/-) mice, while only CD4+ T cells were positively selected and found in the periphery of females. Female A1(M)xRAG- 1(-/-) mice were able to rapidly reject (in <14 days) male (but not female) skin grafts in a CD4-dependent fashion. After multiple grafts, it was confirmed that no CD8+ T cells or surface Ig+ B cells were present. An immunofluorescent analysis of spleen cells after grafting showed that the majority of T cells expressed activation markers (CD44, CD25, and intracytoplasmic IL-2) and a significant proportion were making IFN-γ and IL-4. Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin.

UR - http://www.scopus.com/inward/record.url?scp=0032529407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032529407&partnerID=8YFLogxK

M3 - Article

C2 - 9712055

AN - SCOPUS:0032529407

VL - 161

SP - 1868

EP - 1874

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -