Human CD8+CD28− T suppressor cells expanded by common gamma chain (γc) cytokines retain steady allospecific suppressive capacity in vivo

Abstract

Background: CD8 + CD28 − T suppressor (Ts) cells play critical role in transplant tolerance. Our previous study has generated CD8 + CD28 − Ts cells in vitro which exert robust allospecific suppressive capacity in vitro. Results: CD8 + CD28 − Ts cells were expanded by stimulating human CD8 + T cells with allogeneic antigen presenting cells in the presence of the common gamma chain cytokines IL-2, IL-7 and IL-15 in vitro, and were further verified in vitro through day 7 to 11 for their persistency of the allospecific suppressive capacity. When CD8 + CD28 − Ts cells were adoptively transferred into NOG mice, their capacity to inhibit CD4 + T cell proliferation in allospecific manner remained potent on 11 days after their injection. The mechanisms for expansion of CD8 + CD28 − Ts cells by the common gamma chain cytokines were investigated. These included promoting CD8 + CD28 − T cells proliferation, converting CD8 + CD28 + T cells to CD8 + CD28 − T cells and decreasing CD8 + CD28 − T cell death. Furthermore, the expanded CD8 + CD28 − Ts cells showed upregulation of the co-inhibitory molecule Tim-3 and down-regulation of the cytotoxic molecule granzyme B. Conclusions: In summary, these results demonstrated that the in vitro-expanded human CD8 + CD28 − T cells retained potent allospecific suppressive capacity in vivo and depicted multiple mechanisms for the expansion of Ts cells, which might promote further bench to clinic research.

Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review

“…Simultaneously, costimulatory molecules, CD8 and CD28 provide the second signals for the reaction [5]. Cytokines such as interleukin 2 (IL-2), IL-4, IL-15 and IL-7 are consumed to maintain the later proliferation of activated CD8+ T cells [6,7]. Upon co-stimulation from CD80, CD70, 4-1BB (CD137) and cytokines secreted from Dendritic cells (DCs) such as IL-12, INF-I and IL-15, naïve CD8+ T cells differentiate into cytotoxic T cells (CTLs) [8].…”