A Valujskikh1, C Hartig, P S Heeger. 1. Department of Medicine, Case Western Reserve University and the Louis Stokes Cleveland, Department of Veterans Affairs Medical Center, Ohio 44106, USA.
Abstract
BACKGROUND: Alloreactive CD4 and CD8 T lymphocytes recognize antigen through both the direct and the indirect pathways. Although indirect priming of CD4+ T cells has been well described, little is known about the frequency and cytokine profile of indirectly primed CD8+ T cells during fully allogeneic graft rejection. METHODS: We used a cytokine enzyme-linked immunosorbent spot assay to characterize indirect priming of alloreactive CD8 and CD4 cells in mice. RESULTS: Interferon-gamma-producing CD8+ T cells specific for indirectly presented alloantigen were detectable in allograft-primed mice at a frequency of 50-100 per million cells (compared with 3000 per million for responses through the direct pathway) and were similar in frequency to indirectly primed CD4 cells. CONCLUSION: CD8+ T cells primed through the indirect pathway are a prominent component of the alloreactive T-cell repertoire induced after skin graft placement in mice, raising the possibility that these cells may play a significant role in the rejection process itself.
BACKGROUND: Alloreactive CD4 and CD8 T lymphocytes recognize antigen through both the direct and the indirect pathways. Although indirect priming of CD4+ T cells has been well described, little is known about the frequency and cytokine profile of indirectly primed CD8+ T cells during fully allogeneic graft rejection. METHODS: We used a cytokine enzyme-linked immunosorbent spot assay to characterize indirect priming of alloreactive CD8 and CD4 cells in mice. RESULTS:Interferon-gamma-producing CD8+ T cells specific for indirectly presented alloantigen were detectable in allograft-primed mice at a frequency of 50-100 per million cells (compared with 3000 per million for responses through the direct pathway) and were similar in frequency to indirectly primed CD4 cells. CONCLUSION: CD8+ T cells primed through the indirect pathway are a prominent component of the alloreactive T-cell repertoire induced after skin graft placement in mice, raising the possibility that these cells may play a significant role in the rejection process itself.