Suppression of cell-mediated immune reactivity by peptides cleaved from human fibrinogen

Peptides derived from fibrinogen, known from earlier studies to inhibit the stimulation of lymphocytes in vitro and to suppress the humoral immune response in vivo, were investigated for their effect on cell-mediated immune reactivity in mice. An unfractioned mixture of peptides with molecular weights under 3,500 injected intraperitoneally at repeated intervals suppressed the contact hypersensitivity to oxazolone but did not influence the skin inflammatory reaction to croton oil. Local injections of peptides had a stronger effect on contact hypersensitivity. Four 200 micrograms local injections of peptides prior to sensitization abolished the increase in lymph node weight and the uptake of 125I-iododeoxyuridine in the draining lymph node after sensitization. Three previously isolated peptides with vasoactive effects inhibited Con A-stimulated incorporation of 3H-thymidine into spleen cells. The first, a pentapeptide (Ala-Arg-Pro-Ala-Lys), and the second, an undecapeptide (Ser-Glu-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) both with an enhancing effect on microvascular permeability, were more potent than the third, a pentapeptide with slight vasoconstrictive properties (Thr-Ser-Glu-Val-Lys). Cell viability was not altered, as measured by trypan blue exclusion and the release of 86Rb. Accumulating evidence indicates that peptides derived from fibrin may be of importance as modulators of cellular immunoreactivity in a number of clinical conditions.