Chemokine expression by intraepithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia.
T cells expressing gamma delta TCR may have evolved to recognize Ag in a different manner as well as perform a broader set of functions than T cells with alpha beta TCR. In this study, we tested the hypothesis that dendritic epidermal T cells (DETC) bearing the invariant V gamma 3V delta 1 TCR may be able to signal the migration of peripheral alpha beta T cells to the epidermis by secreting specific chemokines. Expression of macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES, and lymphotactin was inducible in DETC 7-17 cells, whereas mRNA for monocyte chemoattractant protein (MCP)-1 could not be detected. Strikingly, lymphotactin was the most abundant chemokine produced by activated DETC 7-17 cells. Activated primary DETC cultures also produced copious amounts of lymphotactin mRNA. Similarly, freshly isolated and activated intestinal intraepithelial T cells (i-IEL) with gamma delta TCR expressed high levels of lymphotactin mRNA. In contrast, lymphotactin mRNA was present in activated spleen gamma delta T cells at low basal levels. Migration of CD8+ T cells induced by culture supernatants from stimulated DETC 7-17 cells was strongly reduced in the presence of a neutralizing anti-lymphotactin antiserum and to a lesser extent by neutralizing anti-MIP-1 alpha, anti-MIP-1 beta, or anti-RANTES antiserum. The presence of lymphotactin in supernatants from activated DETC 7-17 cultures was directly demonstrated by Western blot analysis. These observations are consistent with a model in which gamma delta IEL play an active multi-faceted role in the maintenance of epithelia homeostasis.
Boismenu
R
R
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Feng
L
L
Xia
Y Y
YY
Chang
J C
JC
Havran
W L
WL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019744:Chemokines, C; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007111:Immunity, Cellular / Q000502:physiology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012260:Ribonucleases / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019744:Chemokines, C; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012795:Sialoglycoproteins; C486249:Xcl1 protein, mouse; C018997:lymphotactin; D012260:Ribonucleases