Donor-specific reactivity and Th1 cytokines--implications for immunologic monitoring.

In their fascinating brief report, van Besouw et al. (1), from Erasmus MC University in Rotterdam, The Netherlands, presented interesting data in renal transplant patients with and without donor-specific hyporeactivity. The Thl cytokines, tumor necrosis factor (TNF)and interferon (IFN), were positively correlated with the presence of detectable donor-specific cytotoxicity, defined as the presence ( 10/10 peripheral blood monocyte cells) of donor-specific cytotoxic T-lymphocyte precursors (CTLpf). Lack of detectable CTLpf was associated with low levels of TNFand IFN. The Th2 cytokines, interleukin (IL)-4, IL-6, and IL-10, were not correlated with CTLpf. The authors concluded that donor-specific hyporeactivity was a function of the absence of Th1 cytokines and was not related to Th2 cytokines. This article offers insights both into the mechanism of donor-specific hyporeactivity and also describes the potential utility of an important immunologic monitoring tool. The observation that reducing Th1 expression is the key association with donor-specific hyporeactivity suggests that targeting this arm of the immune response is of paramount importance, from a clinical point of view. The availability of useful immunologic monitoring is of critical importance in the management of transplant recipients, particularly in the context of attempts to minimize immunosuppression. Traditional reduction of immunosuppression after transplantation has been historically empiric and protocolized formally or informally. Various drug toxicities have suggested the ongoing need to taper immunosuppression: conversely, the development of rejection has signaled the need to intensify immunosuppression. The disadvantages of this approach are obvious, but the development of appropriate immunologic monitoring tools has been limited. The presence of donor-specific antibodies as a marker for subsequent rejection and graft loss has been described by Terasaki and coworkers (2), and attempts have been made to use donor-specific antibody as a marker to intensify immunosuppression (3). On the T-cell side, the Cylex assay has been used as a marker of suppression/ infection (low), optimal immunosuppression (medium), and rejection (high) (4), although its greatest utility may be in the detection of over immunosuppression. Another promising tool to assess T-cell reactivity is the ELISPOT assay to determine the frequency of donor-specific IFNand other cytokineproducing cells. This assay has also been the subject of significant interest and clinical research (5). The demonstration that TNFand IFNcan be potential markers for the presence or absence donor-specific hyporeactivity is a welcome development. What is needed now is a larger scale, multicenter study of these two cytokines, to confirm and amplify these important preliminary findings. Correlation of these markers with the other T-cell and B-cell markers would also be desirable. The group from Rotterdam is to be congratulated for these important observations. Hopefully, additional reports from other centers will soon be available to confirm these interesting findings.