Characterization of epithelial chemoattractants for human intestinal intraepithelial lymphocytes.
OBJECTIVE
Although homing of intraepithelial lymphocytes (IEL) into intestinal epithelia seems to be guided by signals from epithelia, little is known concerning functional epithelial-derived chemoattractants for IEL.


METHODS
Epithelial chemoattractants for IEL were analyzed using chemotaxis chamber system, enzyme-linked immunosorbent assay, and in situ hybridization using human epithelial lines and IEL lines.


RESULTS
Epithelial-conditioned media induced IEL chemotaxis, and this activity was markedly enhanced by prestimulation of epithelia with interferon-(IFN)-gamma. This chemotaxis (stimulation +) was significantly inhibited by neutralizing antibodies to IFN-gamma inducible protein-10 (IP-10) or to monokine induced by IFN-gamma (MIG). Furthermore, while high amounts of IP-10 and MIG were detected in epithelial-conditioned media after IFN-gamma stimulation, equivalent concentrations of recombinant IP-10 and MIG reproduced IEL chemotaxis. Production of IP-10 and MIG in fresh epithelial cells was supported by in situ hybridization and enzyme-linked immunosorbent assay. Lastly, fresh human IEL constitutively expressed CXCR-3 (the common receptor for IP-10 and MIG), and fresh IEL also exhibited chemotaxis to by rIP-10, rMIG, and epithelial-conditioned media.


CONCLUSIONS
Epithelial cells produce chemoattractants for IEL, and such chemokine production is regulated by proinflammatory cytokines such as IFN-gamma. IP-10 and MIG may serve as potentially important epithelial chemokines for IEL, especially under inflammatory conditions.
Shibahara
T
T
Department of Pathology and Laboratory Medicine, Division of Hematology/Oncology, Emory University, Atlanta, Georgia, USA.
Wilcox
J N
JN
Couse
T
T
Madara
J L
JL
D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D003092:Colitis / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000906:Antibodies; D000970:Antineoplastic Agents; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma