Interleukin 2 regulation following semi-allogeneic bone marrow transplantation in mice

Abstract

Success of allogeneic and autologous bone marrow transplantation (BMT) is hampered by susceptibility to infection during the first two post-treatment years. Further, in treating malignant diseases, impaired anti-host reactivity for donor cells may contribute to a high rate of relapse. Both complications are a consequence of immune deficiency involving B and T lymphocytes. The present study evaluates several key parameters of the immunologic reconstitution mechanism in mice subjected to myeloablative total body irradiation following semi-allogeneic (parental) BMT. This resulted in a gradual reduction of splenic CD3, CD4 and CD8 cells until day 45 post-BMT. Concomitantly, there was an increase in monocytes and CD4+/CD8+ (double positive) cells, accompanied by a persistent elevation in the percentage of B lymphocytes. The total thymic and splenic T cell populations were reduced until day +30. The cellular reduction correlated with the poor proliferative response of the thymic and splenic cells. A decrease occurred in IL-2 mRNA expression in thymic cells during days 15-20 post-transplant, corresponding with the low level of IL-2 secretion in the spleen and thymus of the transplanted mice. In conclusion, following semi-allogeneic BMT, there was an overall immune down-regulation in the cells, gene and protein levels. Reduced immunological responsiveness following BMT reinforces the need for improving the immune dysfunction by immunotherapy post-BMT.

Expansion of a restricted residual host Treg‐cell repertoire is dependent on IL‐2 following experimental autologous hematopoietic stem transplantation

“…Lymphopenic conditions in Rag −/− and post-HSCT recipients may differ and our studies examined Foxp3 expressing CD4 + T cells following exposure to TBI, in contrast to non-exposed CD25 + CD4 + T cells in those studies [28]. Despite reduced production of IL-2 following ablation and HSCT [29;30], residual T regs in our studies exhibited robust proliferation. This possibly reflects that unlike naive and memory T cells, which only express the IL-2Rβ and γc chains, T reg cells express CD25 resulting in high affinity IL-2 receptors which better compete for the limited IL-2 present.…”

In Vivo Environment Necessary to Support Transplanted Donor Mouse T Regulatory Cells

“…Although IL-2 is a critical cytokine supporting T reg homeostasis in steady state (17,34,40), ablative conditioning leads to excess IL-7 and IL-15 with very little IL-2 (41)(42)(43)(44). Moreover, IL-7 is an important cytokine for lymphopenic T cell expansion, and together with IL-15, plays a central role in homeostasis of na€ ıve and memory T cells (45)(46)(47).…”