The recruitment of lymphocytes into the skin by T cell lymphokines: the role of gamma-interferon

Abstract

Numerous lymphocytes are recruited from the blood into cutaneous DTH reactions. Alpha/beta-interferon (IFN) and its inducers can recruit lymphocytes into the skin after i.d. injection, but activated T lymphocytes, which are responsible for DTH, produce very little IFN-alpha/beta. Our goal was to determine the major T cell lymphokine (LK) which could stimulate the migration of lymphocytes into the skin. Rats were injected i.d. with LK containing supernatants from activated T cells, and lymphocyte recruitment was measured by the accumulation of 111In-labelled lymphocytes in the skin. Large numbers of labelled cells migrated into sites injected with the LKs. The major portion of the recruiting activity of the LKs coeluted with IFN-gamma after hydroxylapatite and Affigel Blue chromatography, although a second recruiting factor was also found. Both the recruiting and IFN anti-viral activities were partially destroyed by pH 3. A monoclonal anti-IFN-gamma antibody inhibited up to 53% of the recruitment observed after 4 h and up to 43% after 20 h. Kinetic studies showed that maximal recruitment occurred 6 h after i.d. injection of the LKs. Recombinant rat IFN-gamma also stimulated lymphocyte migration into the skin. Histologically, sites injected with IFN-gamma showed a mononuclear cell infiltrate. It is suggested that IFN-gamma is the major mediator of lymphocyte recruitment produced by activated T cells.