Regulation of T lymphocyte trafficking 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 potential to selectively recruit leukocyte subpopulations into sites of inflammation. 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 induced by the hapten, dinitrofluorobenzene (DNFB) in the mouse was used as a model of T lymphocyte trafficking in response to antigenic stimulation. 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 MIP-1 beta mRNAs and proteins. Mast cells accumulating in the nodes during DNFB sensitization were the predominant source of MIP-1 beta, whereas MIP-1 alpha was expressed by multiple cell types. Neutralization of these chemokines profoundly inhibited T lymphocyte trafficking into lymph nodes and altered the outcome of a subsequent challenge to DNFB. Thus, beta-chemokines regulate T lymphocyte emigration from the circulation into lymph nodes during an immune response and contribute significantly to the immunologic outcome.
Tedla
N
N
Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia.
Wang
H W
HW
McNeil
H P
HP
Di Girolamo
N
N
Hampartzoumian
T
T
Wakefield
D
D
Lloyd
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology; D002465:Cell Movement / Q000276:immunology*; D054407:Chemokine CCL4; D003877:Dermatitis, Contact / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D015618:Histiocytosis, Sinus / Q000276:immunology / Q000473:pathology; D006965:Hyperplasia; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007106:Immune Sera / Q000008:administration & dosage; D007264:Inguinal Canal; D007274:Injections, Intraperitoneal; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009929:Organ Size / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000473:pathology / Q000502:physiology*
D054407:Chemokine CCL4; D007106:Immune Sera; D019402:Macrophage Inflammatory Proteins; D004139:Dinitrofluorobenzene