Clonal analysis of T lymphocytes in spleens from patients with Hodgkin's disease. Frequent occurrence of unusual T4-positive cells which co-express cytolytic activity and production of interleukin-2.

T-lymphocyte populations isolated from spleens of untreated patients with Hodgkin's disease (HD) were grown by combining limiting dilution techniques and an assay system that allows clonal proliferation of virtually all human T cells. Under these conditions, high proportions of splenic T lymphocytes (50-80%) underwent clonal expansion, so that the set of clones obtained could be considered representative of the starting T-cell population. A total number of 229 clones from 6 HD spleens (3 uninvolved and 3 histologically involved by the disease) and 133 clones from 3 control spleens (obtained from otherwise healthy individuals, who underwent post-traumatic splenectomy) were examined for surface markers and tested in functional assays. One hundred and seventy-five clones from HD spleens and 75 clones from control spleens expressed the "helper/inducer" (T3+ T4+ T8-)phenotype, whereas as 54 clones from HD spleens and 58 control clones expressed the "cytotoxic/suppressor" (T3+T4-T8+) phenotype. As assessed by a non-specific lectin-dependent lytic assay, the proportion of HD clones displaying cytolytic activity was higher than that of cytolytic clones derived from control spleens. The majority of T4+ clones obtained from HD spleens (either uninvolved or histologically involved by the disease) were cytolytic, whereas only a small proportion (less than 10%) of T4+ clones derived from normal peripheral blood or spleens displayed cytolytic activity. The cytolytic potential of T4+ clones obtained from HD spleens did not reflect the activity of natural killer (NK) cells, since a minority of these clones exerted NK activity on K562 target cells. In addition, most of the T4+ cytolytic clones derived from HD spleens produced particularly high amounts of interleukin-2 (IL-2). These data indicate that T lymphocytes which concentrate in spleens of patients with HD consist at least in part of an infrequent T4+ cell subset co-expressing cytolytic activity and production of IL-2. These cells may reflect a cytotoxic reaction against unknown antigens associated with self class-II histocompatibility antigens.