Jay A. Berzofsky

Effects of Cytotoxic T Lymphocytes (CTL) Directed against a Single Simian Immunodeficiency Virus (SIV) Gag CTL Epitope on the Course of SIVmac239 Infection

ABSTRACT Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency virus-challenged macaques. Therefore, we wanted to test the impact that vaccine-induced CTL responses against an immunodominant Gag epitope might have in the absence of other immune responses. By themselves, these strong CTL responses failed to control SIVmac239 replication.

NKT Cells in Tumor Immunity

NKT cells are a small subset of true T cells that bridge between the innate and adaptive immune systems, provide the cellular immune system with a means to recognize lipid antigens, and interact with and regulate other parts of the immune system. In particular, they regulate tumor immunity both positively and negatively. They are defined by their recognition of lipid antigens presented by the nonclassical MHC molecule CD1d, rather than conventional MHC class I or II molecules. Classical or type I NKT cells use a semi-invariant T cell receptor with a conserved alpha chain in both mice and humans, recognize alpha-galactosylceramide and its homologues, and generally promote tumor immunity. Type II NKT cells use diverse receptors, recognize other lipids such as sulfatide, and usually suppress tumor immunity. These two subsets also cross-regulate each other and influence other immunoregulatory cells. The balance along the axis between type I and type II NKT cells can have profound effects on both innate and adaptive tumor immunosurveillance and tumor immunity, as well as vaccine responses. Harnessing these cells to fight cancer is being undertaken in clinical trials and is beginning to show promise.

Immune Regulation of Tumor Immunity by NKT Cells

While NKT cells comprise only a very small percentage of lymphoctyes, they play very important roles in many disease settings, including cancer. NKT cells can be subdivided into at least two groups that play opposing roles in cancer and also counterregulate each other. While type I NKT cells can promote strong antitumor immunity, type II NKT cells suppress antitumor immune responses and play more of a regulatory role, similar to Tregs and MDSCs. The balance between type I and type II NKT cells can determine whether immune responses to tumors will be activated, resulting in tumor elimination, or will be suppressed, allowing the tumor to grow. Understanding the interactions between NKT cells may aid in the development of new immunotherapies for cancer which can shift the balance of this immunoregulatory axis towards immune activation and tumor killing.