Continuous cultivation of equine lymphocytes: evidence for occasional T cell-like maturation events in horses with hereditary severe combined immunodeficiency.

Abstract

Peripheral blood mononuclear cells (PBMC) from 14 foals with hereditary severe combined immunodeficiency (SCID) were studied to determine the extent of lymphocyte differentiation that occurs in this disorder. PBMC from all 14 horses had the morphologic characteristics of large granular lymphocytes (LGL). Cells from only one of 14 horses were responsive to phytolectin stimulation in a standard blastogenesis assay; however, PBMC from all 14 horses proliferated in continuous culture in the presence of partially purified interleukin 2. Furthermore, there were differences in the growth patterns of these cultured cells that correlated with their ability to respond to phytolectin stimulation. PBMC obtained from the 13 phytolectin-unresponsive foals survived in culture for only 4 to 5 wk, divided very slowly, developed large granules composed primarily of calcium phosphate, and accumulated high concentrations of histamine. In contrast, PBMC from the phytolectin-responsive SCID foal proliferated in continuous culture for over 100 days, divided as rapidly as normal equine PBMC under identical culture conditions, and did not accumulate granules or histamine. These observations indicate that lymphoid cell differentiation occurs in some horses with SCID even though the identity of the LGL is unresolved. Two possibilities are that LGL are products of a pathway separate from that of lymphocytes or that LGL are precursors of mature lymphocytes.