REGULATION OF T-LYMPHOCYTE TRACKING INTO LYMPH-NODES DURING AN IMMUNE-RESPONSE BY THE CHEMOKINES MACROPHAGE INFLAMMATORY PROTEIN (MIP)-1-ALPHA AND MIP-1-BETA

By virtue of their target cell specificity, chemokines have the potent ial to selectively recruit leukocyte subpopulations into sites of infl ammation. Their role in regulation of T lymphocyte traffic into lymph nodes during the development of an immune response has not previously been explored. The sensitization phase of contact hypersensitivity ind uced by the hapten, dinitrofluorobenzene (DNFB) in the mouse was used as a model of T lymphocyte trafficking in response to antigenic stimul ation. Rapid accumulation of CD8(+) and CD4(+) T cells in the draining lymph nodes was closely associated with strongly enhanced expression of macrophage inflammatory protein (MIP)-1 alpha and MLP-1 beta mRNAs and proteins. Mast cells accumulating in the nodes during DNFB sensiti zation were the predominant source of MIP-1 beta, whereas MIP-1 alpha was expressed by multiple cell types. Neutralization of these chemokin es profoundly inhibited T lymphocyte trafficking into lymph nodes and altered the outcome of a subsequent challenge to DNFB. Thus, beta-chem okines regulate T lymphocyte emigration from the circulation into lymp h nodes during an immune response and contribute significantly to the immunologic outcome.