T-lymphocytes play a critical role in both infectious and non-infectious inflammatory reactions involving the lung. While well characterized lymphokines may be involved in neutrophil and monocyte accumulation in the pulmonary compartment, the means by which T-lymphocytes themselves are recruited to the lung is less well understood. Preliminary data suggests that the multifunctional lymphokine interleukin-2 (IL-2) is specifically chemotactic for OKT4+ (helper/inducer) lymphocytes, and that this activity may be mediated by guanosine 3':5'-monophosphate (cGMP).
The aim of the proposed research is to study the mechanism of action of IL2 stimulated lymphocyte locomotion and compare this to its action as a growth factor. The role of cGMP as an intracellular messenger will be assessed directly in stimulated T-lymphocyte subsets in the presence and absence of inhibitors of protein and DNA synthesis by radioimmunoassay. Cyclic GMP analogs and modifiers of guanylate cyclase will be examined for their effects on lymphocyte migration assayed in Boyden chambers and compared with the effects of IL2 in that system. The products of cGMP-dependent protein kinase in T-lymphocytes will next be examined by [P32] incorporation and polyacrylamide gel electrophoresis. The physicochemical properties of these products will be compared to known regulators of cytoplasmic contractile proteins including myosin, actin binding protein, prolifin, filamin, and gelsolin. Adding an understanding of the mechanism of IL2 stimulated lymphocyte migration to its many other activities would contribute to basic science and could help to develop new approaches to treating inflammatory processes in the lung.
