Inflammatory and other factors produced when sensitised lymphocytes are stimulated with antigen

Warrington, Richard John (1973) Inflammatory and other factors produced when sensitised lymphocytes are stimulated with antigen. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

The tuberculin reaction is thought to be a specific immune response by sensitised lymphocytes to the antigen. It is characterised histologically by infiltration with mononuclear leukocytes. -- In experiments described in this thesis, mononuclear leukocytes from peripheral blood of tuberculin-sensitive guinea-pigs, and consisting of greater than 90% small lymphocytes, were stimulated in vitro in serum-free medium with the tuberculin antigen, PPD, for 3 days. The concentrated cell-free supernatants from these cultures produced an inflammatory reaction when injected intradermally into unimmunized guinea-pigs. Supernatants from cultures without antigen did not produce an inflammatory response. The reaction was characterised by erythema and induration reaching a peak at 4-6 hours with perivascular infiltration of polymorphonuclear and mononuclear leukocytes. The supernatants possessing inflammatory activity contained a factor inhibiting the migration of peritoneal macrophages from unimmunized guinea-pigs. -- In experiments in man, it was demonstrated that peripheral blood leukocytes, consisting of 10% lymphocytes and 90% polymorphs from tuberculin-sensitive donors, were inhibited in their movements by the presence of PPD. This inhibition, which did not occur in cells from tuberculin-negative donors, was blocked by 1 uM actinomycin D. In supernatants from PPD-stimulated serum-containing cultures of mononuclear cells from individuals sensitive to tuberculin, there occurred a factor capable of inhibiting the movement of polymorphs. This factor was not produced by cells from tuberculin-negative donors and was not demonstrable in the absence of serum. However, serum-free cultures of peripheral blood mononuclear cells from tuberculin-positive donors when stimulated with PPD released a soluble factor producing erythema and induration when injected intradermally into unimmunized guinea-pigs. This reaction, characterized by an infiltration of mononuclear cells and polymorphs, was maximal at 4-6 hours. There appeared to be a correlation between antigen-specific release of this inflammatory factor and the ability of supernatants to enhance migration of polymorphs.

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