Cellular immune function in uremia: altered cytotoxic and suppressor cell responses to an immunomodulating...

Hemodialysates of uremic patients have been shown by T. Abiko, M. Kumikawa, and H. Sekimo (Biochem. Biophys. Res. Commun. 86, 945, 1979) to contain a heptapeptide which inhibits E-rosette formation by human T cells. This heptapeptide also corresponds to a fragment of beta 2-microglobulin and may play an immunoregulatory role in uremia. We investigated the potential for induction of cytotoxic and suppressor cells by the synthetic heptapeptide (HP) in blood lymphocytes of normal donors and uremic patients. Cytotoxic activity of normal lymphocytes was significantly enhanced by low concentrations of HP while high concentrations depressed it. Two patterns of responsiveness were observed among uremic patients: a high responder group reacted similarly to normals, whereas a low responder group showed little reactivity to HP. Removal of the NH2-terminal histidine of the heptapeptide strongly diminished its enhancing activity on normal cytotoxic cells while maintaining activity on uremic lymphocytes. When HP and des-His-HP were studied as possible inducers of suppressor cell activity, only the latter was found to be active on normal cells. Lymphocytes from uremic patients failed to respond to either HP or des-His-HP in suppressor cell generation. It is suggested that continuous interaction between lymphocytes and high concentrations of HP or des-His-HP in uremia may have altered their sensitivity to the immunomodulatory effects of the peptides and may be instrumental in the immune deficiency associated with renal failure.