Lymphocyte recruitment in delayed-type hypersensitivity. The role of IFN-gamma.
Lymphocytes are recruited out of the blood into delayed-type hypersensitivity (DTH) reactions, but the factors controlling their migration are poorly understood. Our previous studies have shown that IFN-alpha/beta, its inducers, and T cell lymphokines can induce lymphocyte migration into the skin after intradermal injection. The present studies were designed to determine the effect of rIFN-gamma, IL-1, and anti-IFN-gamma on lymphocyte recruitment into DTH. Small peritoneal exudate lymphocytes, which preferentially migrate to inflammatory sites, were labelled with 111In and injected i.v. into rats. The intradermal injection of IFN-gamma stimulated the migration of these lymphocytes into the skin. IL-1 induced very little migration by itself, but enhanced the effect of IFN-gamma. Kinetic analysis demonstrated that the migration of lymphocytes to IFN-gamma was rapid, with a peak at 6 h, whereas migration into a DTH reaction was minimal for the first 8 h and reached a peak 24 h after intradermal injection. Polyclonal rabbit anti-IFN-gamma anti-serum, and a Mab to IFN-gamma, DB-2, could almost completely block lymphocyte migration induced by IFN-gamma. Furthermore, DB-2 inhibited lymphocyte recruitment into DTH reactions by 50 to 90%. This Mab did not affect migration in response to IFN-alpha/beta, although it partially inhibited the response to polyI:C. The effect of IFN-gamma on lymphocyte recruitment was not specific for small peritoneal exudate lymphocytes, because both spleen T cells and lymph node cells migrated in response to IFN-gamma and DB-2 inhibited the recruitment of splenic T cells to DTH. Thus, IFN-gamma is a potent stimulator of lymphocyte migration into the skin and a major mediator of lymphocyte recruitment into DTH.
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007158:Immunologic Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D007375:Interleukin-1; D011994:Recombinant Proteins; D007371:Interferon-gamma