Clonal priming of human lymphocytes with soluble microbial antigens: high-dose paralysis, restoration, and autologous leukocyte preference.

Lymphocytes stimulated in appropriate leukocyte cultures undergo blastogenesis and proliferation for a finite period of time. With specific antigens the proliferative response peaks usually between 4 and 8 days, after which the blastoid cells revert to small lymphocytes. Lymphocytes "primed" in this manner can be restimulated to proliferate only by the same antigen with which they were incubated and only with an adequate amount of a self-specific, autologous, somatic product(s). First or "primary" leukocyte cultures stimulated by optimal or supraoptimal concentrations of soluble protein antigens (purified protein derivative (PPD), tetanus toxoid, Candida albicans) will undergo proliferation in the first culture, but the increased number of small lymphocytes that can be visualized after 10--14 days often fail to respond to any stimulus in second (secondary) or "primed" cultures. However, when fresh X-irradiated autologous cells are re-added in appropriate amounts, vigorous accelerated proliferation takes place. Addition of allogeneic cells to antigen-primed populations has one of three effects: (1) no effect (complete restriction); (2) in some instances allogeneic cells restore a significant response to the specific antigen but almost never to the same degree as autologous cells; and (3) allogeneic cells can also induce high levels of accelerated responsiveness without added antigen. These findings are discussed in the context of a working hypothesis that self-specific factors are involved in all specific immune responses. The combination of antigen and self-specific factors may lead to a quantitatively unique immune response to all antigens in each individual. The preferential response to antigen in conjunction with autologous rather than allogeneic leukocytes suggests that self-specific products are required for recognition of soluble microbial antigens.