Ultrastructural analysis of HNK-1+ cells in human peripheral blood and lymph nodes

HNK-1 positive (HNK-1+) cells in human peripheral blood and lymph nodes were comparatively analysed by means of immunohistochemistry and immunoelectron microscopy. In peripheral blood, the HNK-1+ cells were grouped into large granular lymphocytes (LGLs), small lymphocytes and intermediate forms, all of which had many fine cytoplasmic processes. Except for smooth-surfaced lymphocytes, they could not be distinguished from helper/inducer T (OKT4/Leu3a) cells and suppressor/cytotoxic T (OKT8/Leu2a) cells. In double staining, HNK-1+T3- cells and HNK-1+T3+ cells could not be clearly distinguished in terms of morphology, although the former contained many LGLs. The HNK-1+ cells in the lymph nodes accumulated in the light zones of the germinal centers (GCs). These cells were small to medium-sized lymphocytes with few electron-dense granules and exclusively co-expressed helper/inducer T cell antigens (HNK-1+T4+). Their cytoplasmic projections were interwoven with those of the follicular dendritic cells which trap immune complexes for a long duration. These configurations suggest that HNK-1+T4+ cells in GCs are engaged in an immunological regulation of germinal center cells. On the other hand, large blastic HNK-1+ cells were scattered outside the GCs and some of them were in the process of mitosis. Furthermore, HNK-1+LGL-like cells with a few large electron-dense granules were rarely seen. These observations indicate that the HNK-1+ cells in the lymph nodes may proliferate outside GCs and differentiate into LGLs with a strong natural killer function.