Cytokine Secretion and Noncytotoxic Functions of Human Large Granular Lymphocytes

Abstract

The natural killer (NK) activity against tumor- and virus-infected cells is exerted by a distinct group of peripheral blood leukocytes with morphological characteristics of large granular lymphocytes (LGLs). There is also considerable evidence that LGLs may play a critical role in the in vivo resistance against bone marrow allografts and primary oncogenesis as well as tumor metastases. G. Trinchieri and co-workers first reported in 1977 that human lymphocytes may be stimulated by some tumor cell lines to produce interferons (IFN). This initial observation was later extended by showing that production of IFN was also induced by virus-infected allogeneic fibroblasts. The positive self-regulatory role of the cytokine production by LGLs is further supported by data obtained with subsets of LGLs and with LGL clones, suggesting that both NK activity and secretory functions may coexist in some individual cells. However, the data also indicate that noncytotoxic subsets and clones of LGLs could produce IL-2 and/or IFN-γ.