In vitro T cell proliferation from kidney allograft biopsies with unremarkable pathology: new strategies for an old problem.

Acute rejection of renal allografts is mediated by infiltrating alloreactive T cells. The goals of this study were to correlate T cell proliferation with rejection and to determine whether T cell proliferation in the absence of rejection would predict future rejection episodes. Toward this, kidney biopsies (n=100) were cultured in the presence of interleukin-2. Cultures were examined at 4, 24, and 48 hr for T cell proliferation. A strong correlation was observed between T cell proliferation at any time point and rejection. There was not a significant correlation between T cell proliferation in biopsies with no rejection and the occurrence of a rejection episode within 2 months. However, T cell proliferation after 4 hr was a better predictor of the occurrence of rejection within 2 months compared with observations after 24 and 48 hr. Therefore, a subgroup of patients with unremarkable biopsies but T cell proliferation may be at risk for rejection and warrant closer observation and possible tailoring of immunosuppression.

Correlation between interleukin-15 and granzyme B expression and acute lung allograft rejection.

The levels of interleukin (IL)-15 and granzyme B mRNA expression have been correlated with acute rejection episodes of kidney and heart allografts. Thus, the purpose of this study was to determine whether a correlation exists between the expression of IL-15 and granzyme B and acute lung allograft rejection. Toward this, the levels of IL-15 and granzyme B mRNA expression were determined in bronchoalveolar lavage-derived alveolar macrophages and total cells, respectively, from lung transplant patients with stable lung allograft function and patients undergoing acute rejection episodes. The expression levels of IL-15 mRNA was significantly higher in the patients undergoing acute rejection as compared to patients with stable lung function (P=0.02). The expression levels of granzyme B mRNA was also significantly higher in the patients undergoing acute rejection as compared to patients with stable lung function (P=0.005). The Receiver-Operating-Characteristic curve demonstrated that acute rejection can be predicted with a sensitivity of 94% and specificity of 67% with the use of a cutoff value of 3.1 fg of granzyme B mRNA per microgram of total RNA (or 71% sensitivity and 75% specificity of a cutoff value of 9.1 fg/microg). These data indicate that IL-15 secreted by activated alveolar macrophages and granzyme B secreted by activated CD8+ cytotoxic T lymphocytes play important roles in the process of acute lung allograft rejection.