The IL-2 mediated amplification of cellular cytotoxicity.
High dose [greater than 1 nM or 30 IU] interleukin-2 (IL-2) can induce MHC-unrestricted killing from various lymphoid populations. Although it is well established that CD16+ NK cells are the major source of blood-derived LAK precursors, other lymphoid cells, including several CD3+ T subsets can be a source of precursor activity. We hypothesize that most, if not all, lymphocytes with cytolytic potential may eventually express MHC-unrestricted killing, when provided with adequate IL-2 to initiate required secondary cytokine production. This perspective article presents our cumulative data supporting the role of secondary cytokines in the IL-2 initiated activation of MHC-unrestricted killing, first by our observations of synergy with the exogenously added TNFs or IL-1s in combination with low dose IL-2, and then by the evidence of endogenous cytokine production and response in lymphocytes stimulated with high dose IL-2. Understanding the amplification mechanism(s) of the various effector arms of the immune system is critical to the eventual regulation of graft rejection, autoimmune phenomena, and potentially to the treatment of cancer. Our studies have focused on the cytotoxic lymphocyte effector system, and have addressed the molecular pathways by which IL-2 induced cytokines influence the quantity and quality of the cytotoxic lymphocyte response. This article will review the pivotal role that IL-2 plays in the development of CTL (MHC-restricted antigen-specific cytotoxic lymphocytes), followed by the description of how studies in the CTL system led to the observation that IL-2 alone can activate a heterogeneous collection of MHC-unrestricted killer lymphocytes, originally known as "Lymphokine Activated Killers" or LAK.(ABSTRACT TRUNCATED AT 250 WORDS)
Grimm
E A
EA
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Owen-Schaub
L
L
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2