The Cultured Lymphocyte in Clinical and Experimental Medicine

Abstract

Our understanding of the nature of the lymphocyte and its role in health and disease
has undergone dramatic changes in the last decade. Known for almost one hundred years,
peripheral lymphocytes had traditionally been considered short-lived with limited
biologic activity and of little significance to the economy of the host. Recent studies,
however, have clearly demonstrated that the circulating lymphocyte pool is composed
of a spectrum of cells of varying origins, lifespans, fine structural features and capacities
to mediate immunologic responses (1). A fortuitous observation by Nowell in 1960 (2)
was a major impetus for this continuing series of investigations in lymphocyte biology.
He noted that phytohemagglutinin (PHA), a crude extract of the common red kidney
bean, had the remarkable ability to cause normal small lymphocytes from peripheral
blood to undergo a series of morphologic changes to "blast like» cells in tissue culture.
A variety of immunologic and non-immunologic stimuli were subsequently shown to
initiate similar morphologic alterations in small lymphocytes associated with new RNA,
protein, and DNA synthesis, followed by mitosis and cell division (3). This process,
termed lymphocyte transformation, confirmed that the lymphocyte is a resting cell
capable of further differentiation and proliferation and provided an exceedingly ver

satile and accessible in vitro model for the orderly analysis of human immunologic
reaction, genetic variation, and cellular differentiation. The profound impact of this
discovery on medical genetics, immunology, cell biology and biochemistry is immeasurable,
recognized by clinicians and researchers alike. Work with lymphocytes in short
term culture and in the more recently developed established suspension cultures has produced
a wealth of information to be assimilated and put to use. The versatility of these
systems for the detection, definition, an'd solution of problems in clinical and experimental
medicine has been gratifying and the limits of their potential usefulness are yet to be
defined. Our Progress in Lymphology will highlight some of the advances made possible
by the study of cultured lymphocytes and will consider new directions for future research
and clinical application.