Activation of Human Lymphocytes

Lectins and other polyclonal lymphocyte stimulants have been used extensively both to analyze early events in cellular activation and clinically as aids to the assessment of immunocompetence (1-5). Earlier studies of the response of human blood lymphocytes to lectins provided suggestive evidence for heterogeneity of responding lymphocyte populations (6, 7). Chessin et al. (6) showed that the lymphoblast population evident in pokeweed mitogen (PWM) 1 (Phytolacca americana) were separable into two broad catagories; type I cells which were indistinguishable from virtually all lymphoblasts activated by phytohemagglutinin (PHA) (Phaseolus vulgaris), and type I I cells which could not be found in PHA cultures and were distinguished by their higher cytoplasm to nucleus ratio, and lack of periodic acid-Schiff-positive (presumably glycogen) granules. These observations were made at a time when the dichotomy of lymphocytes into T and "bursal"-equivalent-derived (B) axis differentiation pathways (8) was not fully appreciated. Nevertheless, subsequent studies strongly supported the interpretation that T cells responded to PHA whereas both T and B responded to PWM. In particular, analyses of the proliferative and biosynthetic responses to PHA and PWM with lymphocytes from both normal donors (9) and patients with selective immunodeficiencies (10-12) provided compelling support for the view that lectins could selectively trigger T and/or B lymphocytes. This concept has been established beyond question in animal model systems, particularly for the chicken (13-15) and mice (3, 4, 16) where appropriate manipulations are feasible and definitive cell markers and cell separation techniques are available. In mice for example, soluble PHA stimulates T cells, lipopolysaccharide (LPS) B cells, and PWM T plus B cells. This selectivity may require some qualification, however, in terms of the culture conditions used and timing of the experiment and more especially of cellular interactions when T and B cells (plus macrophages) are mixed together. Recently, marker systems and separation methods have become available which permit the identification and purification of human Tand