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
SN - 0022-1767
VL - 161
SP - 1868
EP - 1874
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -