Gammadelta T cells in EAE: early trafficking events and cytokine requirements.
We have previously shown that gammadelta T cells traffic to the CNS during EAE with concurrently increased expression of beta(2)-integrins and production of IFN-gamma and TNF-alpha. To extend these studies, we transferred bioluminescent gammadelta T cells to WT mice and followed their movement through the acute stages of disease. We found that gammadelta T cells rapidly migrated to the site of myelin oligodendrocyte glycoprotein peptide injection and underwent massive expansion. Within 6 days after EAE induction, bioluminescent gammadelta T cells were found in the spinal cord and brain, peaking in number between days 10 and 12 and then rapidly declining by day 15. Reconstitution of gammadelta T cell(-/-) mice with gammadelta T cells derived from beta(2)-integrin-deficient mice (CD11a, -b or -c) demonstrated that gammadelta T-cell trafficking to the CNS during EAE is independent of this family of adhesion molecules. We also examined the role of gammadelta T-cell-produced IFN-gamma and TNF-alpha in EAE and found that production of both cytokines by gammadelta T cells was required for full development of EAE. These results indicate that gammadelta T cells are critical for the development of EAE and suggest a therapeutic target in demyelinating disease.
Wohler
Jillian E
JE
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Smith
Sherry S
SS
Zinn
Kurt R
KR
Bullard
Dan C
DC
Barnum
Scott R
SR
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D018845:CD11 Antigens / Q000235:genetics; D018821:CD18 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology*; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D018845:CD11 Antigens; D018821:CD18 Antigens; D016207:Cytokines; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma