Regulation of Secondary Antigen-Specific CD8+ T-Cell Responses by Natural Killer T Cells

Abstract

The physiologic function of natural killer T (NKT) cells in adaptive immunity remains largely unknown because most studies have used NKT cell agonists. In the present study, the role of NKT cells during the secondary effector phase was investigated separately from the primary immunization phase via adoptive transfer of differentiated effector T cells into naive recipients. We found that secondary antitumor CD8 + T-cell responses were optimal when NKT cells were present. Tumor-specific CD8 + effector T cells responded less strongly to tumor cell challenge in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT cell-mediated enhancement of the secondary antitumor CD8 + T-cell response was concurrent with increased number and activity of tumorspecific CD8 + T cells. These findings provide the first demonstration of a direct role for NKT cells in the regulation of antigen-specific secondary T-cell responses without the use of exogenous NKT cell agonists such as A-galactosylceramide (A-GalCer). Furthermore, forced activation of NKT cells with A-GalCer during the secondary immune response in suboptimally immunized animals enhanced otherwise poor tumor rejection responses. Taken together, our findings strongly emphasize the importance of NKT cells in secondary CD8+ T-cell immune responses. [Cancer Res 2009;69(10):4301-8]

NKT Cell-Dependent Regulation of Secondary Antigen-Specific, Conventional CD4+ T Cell Immune Responses

“…Recently, we demonstrated that NKT cells play an essential role during the secondary immune response of CD8 + T cells by inducing the expansion and activation of effector CD8 + T cells (13). Based on these results, we hypothesized that NKT cells would also contribute to the secondary immune response of CD4 + T cells.…”

“…FACS staining was performed as previously described (13). Briefly, cells preincubated with the anti-FcgRII/III mAb 2.4G2 for 30 min were stained with the appropriate combinations of the following mAbs: anti-CD4, anti-TCR-b, anti-DO11.10 TCR, anti-CD45.1, anti-CD3ε, anti-IL-4, and anti-IFN-g (all from BD Pharmingen).…”

“…Ag-specific, adaptive T cell responses in both defense and pathogenesis consist of a relatively weak primary immune response and a stronger secondary immune response mediated by activated or memory T cells on Ag rechallenge. Although it has recently been shown that a successful CD8 + T cell-mediated secondary immune response to Ag is dependent on the presence of NKT cells (13), it is not clear whether NKT cells also contribute to CD4 + T cellmediated secondary immune responses.…”

The requirement of natural killer T-cells in tolerogenic APCs-mediated suppression of collagen-induced arthritis

“…In contrast, a recent report clearly demonstrated that NKT cells strengthen and optimize ongoing immune responses of antigen-specific CD8 + cytotoxic T lymphocytes, (Hong et al, 2009) as well as pre-established Th1 and Th2 CD4 + T cells (Shin et al, 2010).…”

“…However, there are enough data supporting the role of NKT cells in the pathogenesis of autoimmune joint inflammation, such as seen in CIA (Chiba et al, 2005;Kim et al, 2005). Our previous study also showed that NKT cells are associated with acceleration and perpetuation of arthritic disease in a DBA/1 genetic background (Jung et al, 2009). Although the effects of Tol-APCs and NKT cells on CIA have been investigated independently, their coordinated functions have not been studied.…”