Certain inflammatory reactions in the lung are characterized by a predominance of lymphocytes, yet the mechanism by which effector lymphocytes are recruited to sites of inflammation is not well understood. Monocytes and neutrophils can be recruited through the production and interaction of chemoattractant and migration inhibitory lymphokines. Studies from our laboratory have recently elucidated an analogous system for human T lymphocytes - a lymphocyte chemokinetic factor (LCF) and two non-cytotoxic lymphocyte migration inhibitory factors (LyMIF75K and LyMIF35K) produced by histamine receptor-bearing human blood T lymphocytes in response to histamine, a vasoactive product of tissue mast cells and basophils. The mechanism(s) by which migration inhibition is effected is not known, though there is evidence that at least one of the LyMIFs (LyMIF35K) works through the medium of a specific cell-membrane receptor. The effect of LyMIFs on lymphocyte metabolic or cytoskeletal, and thus motile, function is not yet known. I propose to investigate the cell of origin, physicochemical characteristics and biologic activity of LyMIF75K and LyMIF35K. Utilizing standard separation techniques, LyMIFs produced by human blood lymphocytes and T-T hybridomas will be purified to homogeneity. Using purified material, I will investigate the effect of these lymphokines on lymphocyte subsets. Radiolabeled LyMIFs will be produced, and this material used to investigate LyMIF-cell membrane receptor interactions. Selective activation of resident or infiltrating histamine receptor-bearing T lymphocytes to produce LCF and LyMIFs may explain the recruitment and immobilization of effector lymphocytes to inflammatory sites in the lung. An understanding of the variables affecting LyMIF production and actions on target T lymphocytes may result in new approaches to therapy of some lymphocyte-mediated inflammatory lung diseases.
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