Immunoexpression of perforin and granzyme B on infiltrating lymphocytes in human renal acute allograft rejection

• Autores: M. Danilewicz, M. Wagrowska Danilewicz
• Localización: Nefrología: publicación oficial de la Sociedad Española de Nefrología, ISSN 0211-6995, Vol. 23, Nº. 6, 2003, págs. 538-544
• Idioma: inglés
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• Resumen

  • Graft destruction can be effected by direct cell-to-cell contact between acti-vated effector T cell and a target graft resulting in delivery of cytotoxic mole-cules.

    Perforin and granzyme B can be used as activation markers for cytoto-xic cells in allograft tissue. The aim of the study was to determine the immunoexpression of perforin and granzyme B by immune cells infiltrating renal tissue during acute allograft rejection and to evaluate any correlation bet-ween the phenotype of infiltrating lymphocytes and cells expressing cytotoxic granules as well as the severity of graft damage as defined by Banff 97 crite-ria.

    Immunoperoxidase staining was carried out using monoclonal antibodies anti- perforin, -granzyme B, -CD3 and -CD8 on renal allograft biopsy speci-mens from twenty one patients with acute renal transplant rejection: Banff 97 IA (n = 11) and Banff 97 IB (n = 10). As a control 11 biopsy specimens of renal transplant patient without any signs of rejection were used. All allograft biopsy specimens with acute renal transplant rejection contained a high number of CD3 + T cells (Banff IA: 437.4 ± 154.4 and Banff IB: 825 ± 339.9 vs 123.4 ± 52.5 in controls) and CD8 + T lymphocytes (Banff 97 IA: 177.6 ± 89.2 and Banff IB: 293.2 ± 112.4 vs 64.2 ± 37.1 in controls). Immunostaining for granzy-me B and perforin was negative in controls. The immunopositivity for perforin was similar in Banff IA and Banff IB acute allograft rejection (1.5 ± 0.6 vs 1.8 ± 0.8, respectively). Granzyme B+ cell count was significantly higher in seve-re rejection group Banff IB (128.3 ± 74.3) than in Banff IA group (48.2 ± 18.3).

    Moreover, in acute allograft rejection Banff IB the number of granzyme B+ cells and perforin+ cells was correlated with the number of CD8 + T cells. In con-clusion, our results suggest that in acute tubulointerstitial allograft rejection ac-tivated cytotoxic T lymphocytes play a major role. The strong immunopositi-vity for granzyme B on infiltrating cells in renal transplant tissue is suggested as a marker of severity of graft damage.