MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines.
We analyzed for the first time the expression of chemokines in subpopulations of the murine immune system at the single-cell level. We demonstrate in vitro and in a model of murine listeriosis that macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), and activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin are cosecreted to a high degree with IFN-gamma by activated individual natural killer (NK), CD8(+) T, and CD4(+) T helper 1 (Th1) cells. Functionally, ATAC and the CC chemokines cooperate with IFN-gamma in the up-regulation of CD40, IL-12, and tumor necrosis factor-alpha, molecules playing a central role in the effector phase of macrophages. Our data indicate that (i) MIP-1alpha, MIP-1beta, RANTES, and ATAC are not only chemoattractants but also coactivators of macrophages, (ii) MIP-1alpha, MIP-1beta, RANTES, and ATAC constitute together with IFN-gamma a group of "type 1 cytokines," and (iii) these cytokines act together as a functional unit that is used by NK cells in the innate phase and then "handed over" to CD8(+) T cells in the antigen-specific phase of the immune defense, thus bridging the two components of a Th1 immune reaction.
Dorner
Brigitte G
BG
Molecular Immunology, Robert Koch-Institute, D-13353 Berlin, Germany.
Scheffold
Alexander
A
Rolph
Michael S
MS
Huser
Martin B
MB
Kaufmann
Stefan H E
SH
Radbruch
Andreas
A
Flesch
Inge E A
IE
Kroczek
Richard A
RA
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism*; D019744:Chemokines, C; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism; D008089:Listeria monocytogenes / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019744:Chemokines, C; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; C486249:Xcl1 protein, mouse; C018997:lymphotactin; D018664:Interleukin-12; D007371:Interferon-gamma