IDENTIFICATION OF NATURAL SUPPRESSOR CELLS IN LONG-TERM RENAL-ALLOGRAFT RECIPIENTS

We have previously reported an abnormal expansion of CD3+Leu7+ (CD57+) large granular lymphocytes in long-term renal allograft recipients. These cells lacked NK activity, T-helper activity and did not respond to T cell mitogens. The following studies were done in order to further define the functional characteristics of these cells. We sorted CD3+Leu7+ T cells from the peripheral blood of 45 recipients (all with good renal allograft function), and found that these cells suppress mixed lymphocyte culture responses and pokeweed mitogen-induced IgG secretion in a non-genetically restricted manner. PWM-induced IgG secretion assays are suppressed by 60-100%, and MLC responses are suppressed by 20-85% at a ratio of 1:10 CD3+Leu7+ cells to responder/effector cells. Supernatants from CD3+Leu7+ cell cultures are also suppressive. On the other hand, unsorted cells and non-CD3+Leu7+ sorted cells either enhance responses or produce less than 10% suppression under the same conditions. Patients who were tested more than once showed a relatively stable percentage and suppressive effect of their CD3+Leu7+ cells over an interval of 6-12 months. These nonspecifically suppressive CD3+Leu7+ large granular lymphocytes are similar in many ways to the natural suppressor cells that have been identified in hematopoietic tissues, in graft-vs.-host disease, and in the lymphoid organs of neonates.