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

125 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zelenika, D., Adams, E., Mellor, A., Simpson, E., Chandler, P., Stockinger, B., Waldmann, H., & 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.