High frequency of IL-4 producing helper T lymphocytes associated with a reduced incidence of heart allograft rejection

Abstract

The reduction in the frequency of rejection episodes several months after heart transplantation (HTX) correlates with the development of donor-specific nonresponsiveness. This is reflected in a reduced frequency of donor-specific cytotoxic T cells (CTL) in the peripheral blood. We investigated whether the reduced CTL frequency and the incidence of rejection episodes coincided with a change in the frequency of either IL-2- or IL-4-producing helper T lymphocytes (HTL). We measured the frequency of HTL before and at several time points after HTX in the blood of ten recipients, using limiting dilution analysis for IL-2 and IL-4. In most patients, HTL frequencies dropped immediately after transplantation, but returned to pre-HTX values later after transplantation. No consistent decrease or increase in frequencies was observed long after HTX. In contrast to IL-2, the HTL frequencies for IL-4 before transplantation were significantly higher in patients without post-HTX rejection episodes requiring treatment than in patients with such episodes. This phenomenon was observed for the in vitro responses towards both donor and third-party cells. In conclusion, relatively high frequencies of IL-4-producing T cells may have a beneficial effect on the outcome of human heart transplantation, because they are associated with a reduced incidence of rejection episodes after transplantation.

T-Cell autoreactivity to Hsp in human transplantation may involve both proinflammatory and regulatory functions

“…For example, a higher frequency of alloreactive IL-4 producing cells in the pre-Tx period has been associated with a decrease in rejection episodes, in human heart transplantation [53]. A specific low producer single nucleotide polymorphism (SNP) in the promoter of IL-4 gene was significantly increased in the rejector group when present in renal transplant recipient/ donor pairs [54].…”

Immunologic monitoring

“…Our laboratory has data to support the assertion that the frequency of IFN‐γ‐secreting CD8 + T cells is of value in measuring the alloresponses to HLA class I disparities in unrelated donor hematopoietic cell transplantation (Brookes and Lechler, unpublished observations). There have also been claims that raised frequencies of T alloreactive T cells secreting the Th2 cytokine, IL‐4, are associated with a better outcome in heart (44) and bone marrow transplantation (45). Further development in the detection of cytokines may help in dissecting mechanisms of tolerance and rejection.…”

“…Direct pathway responses have been the subject of a number of studies. Donor‐specific cytotoxic T‐cell hyporesponsiveness that develops sometime after kidney (52), heart (44, 45, 126), or lung (10) transplantation has been described. However, as before, this finding has not been universal (53,127–129).…”

Cardiovascular diabetology in the core of a novel interleukins classification: the bad, the good and the aloof

“…In heart transplant recipients, relatively high frequencies of IL-4-producing T cells have a beneficial effect on the outcome, being associated with less rejection episodes [44]. This is manifested by IL-4 production within the donor heart, mainly by mast cells, and also by fibroblasts present in the donor's stromal elements [45]. Concerning diabetes, children with parents with type 1 diabetes demonstrated an impairment in the ability to produce the IL-4 related immunoglobulin G4 antibody response to tetanus toxoid [46].…”