Studies done on lymphocyte priming and re-stimulation in secondary culture demonstrated a similar but logarithmically greater paradoxical pattern.1 We found that the optimal antigenic stimulating concentration in the primary culture of leucocytes from a sensitive donor, using tetanus toxin, led to unresponsiveness in secondary culture seven days later. Greater secondary lymphocyte reactivity, measured as blastogenesis by radioactive thymidine incorporation, occurred as we progressively lowered the stimulating concentration to one thousandth the optimal primary stimulating concentration (see Figure 1).4 Our later studies demonstrated that a feeder layer of irradiated autologous leukocytes could restore the secondary culture response to optimal primary culture antigen levels.5,6
One possible explanation is that we saturated the HLA-D antigen presenting and receptor sites so that lymphocytes could not be activated. It is also possible that we induced antiidiotype immunity. The concept is that with such a large dose of the specific stimulating antigen, a huge number of reactive lymphocytes are induced with the same or similar receptors recognizing that antigen early on. Subsequently, in that same culture, remaining lymphocytes develop receptors against the anti-tetanus toxoid receptor bearing cells in the culture. This possibility is further suggested by our later demonstration of specific suppression of response to microbial antigens by stimulated cells.7 Work by others has also confirmed this possibility.8,9 T-cells are involved in Covid-19 immunity directly as evidenced by studies of convalescent Covid-19 patients.