Donor IL-6 deficiency evidently reduces memory T cell responses in sensitized transplant recipients

Resistance of tolerance induction in sensitized transplantation is mainly caused by generation of memory T cells. It is unknown whether alteration of graft niche such as level of pro-inflammatory cytokines can affect generation of memory T cells.

IL-6 deficient or wild-type (WT) C57BL/6 heart grafts were transplanted into pre-sensitized wild-type BALB/c recipients. Frequencies of memory T cells in the peripheral blood, grafts, and spleen were evaluated.

We revealed that deficiency of donor IL-6 could significant prolong sensitized allograft survival. Compared with counterpart of WT group, frequency of effector memory CD4 + T cells (CD4 + CD44 + CD62L-) in the peripheral blood was significantly lower in the IL-6 KO group (p = .026) at day 3 post-transplantation. Frequency of effector memory CD8 + T cells (CD8 + CD44 + CD62L-) in the peripheral blood was significantly lower in the IL-6 KO group (p < .0001) at day 3 post-transplant in comparison to that of WT group. No significant difference of central memory T cells was found between these groups. Histology demonstrated that deficiency of donor pro-inflammatory cytokine IL-6 (IL-6 KO group) preserved cardiac architecture with a mild infiltration of lymphocytes, whereas wild-type donor (control group) caused an evident lymphocytic infiltration within myocardial fibers of grafts and destruction of cardiac structure.

Deficiency of pro-inflammatory IL-6 of donor graft could effectively prolong sensitized allograft survival, which was caused by a remarkable decrease of peripheral memory T cells rather than central memory T cells. This unveiled mechanism of targeting IL-6 signaling pathway might provide a novel insight into preventing allograft rejection for sensitized transplant recipients.