MHC restricted and non-restricted killer lymphocytes

Abstract

Cytotoxic lymphocytes are either MHC-restricted (cytotoxic T-cells) or nonrestricted (natural killer NK-cells), although cells of the monocyte/macrophage lineage are also cytotoxic, and lymphocytes or phagocytic cells expressing Fc-receptors for immunoglobulin can function as antibody-dependent killer cells (referred to as antibody-dependent cellular cytotoxicity: ADCC). Antigen-specific T-lymphocytes recognise their target antigen in the context of MHC class I components, focusing their attack only against those cells expressing the relevant antigen specificity on their cell surface. A more primitive and alternative mechanism exists whereby NK-cells, classified as large granular lymphocytes (LGL), are able to kill in a non-specific manner, not requiring prior sensitisation to antigen. Both antigen-specific T-cells and LGL mediate their cytotoxicity through the release of cytotoxic molecules at the target-effector cell interface. LGL also have a regulatory role in the immune system through the release of cytokines, and can be distinguished from T-lymphocytes by the expression of distinct phenotypic markers (CD16+, CD56+) and they lack CD3 antigen expression or rearranged alpha/beta or gamma/delta T-cell receptor gene products. Cytotoxic activity is positively regulated by interleukin-2 (IL-2) and interferon (IFN), whilst prostaglandins and transforming growth factor-beta (TGF beta) diminish activation and effector pathways. Cytotoxicity mediated by NK- and T-cell populations are principally involved in the defence against microbial infections and neoplasia; the abrogation of cytotoxicity either by direct interaction of 'suppressor factors' with effector cells, or indirectly by reducing cytokine production can inevitably lead to the proliferation of the disease.