Regulation of chronic colitis in athymic nu/nu (nude) mice.
The objective of this study was to assess the roles of NK cells, B cells and/or intraepithelial lymphocytes (IEL) in suppressing the development of colitis in nude mice reconstituted with CD4(+)CD45RB(high) T cells. BALB/c nude mice were lethally irradiated and reconstituted with bone marrow from different immunodeficient mice to generate athymic chimeras devoid of one or more lymphocyte populations. Transfer of CD4(+)C45RB(high) T cells into chimeric recipients devoid of B cells, T cells and IEL produced severe colitis within 6-8 weeks, whereas transfer of these same T cells into B cell- and T cell-deficient or T cell-deficient chimeras produced little to no gut inflammation. In addition, we found that nude mice depleted of NK cells or RAG-1(-/-) mice reconstituted with IEL failed to develop colitis following transfer of CD45RB(high) T cells. Severe colitis could, however, be induced in nude mice by transfer of activated/T(h)1 CD4(+)CD45RB(low) T cells. Taken together, our data suggest that IEL, but not B cells or NK cells, play an important role in suppressing the development of chronic colitis in this model. In addition, our data demonstrate that suppression of disease may be due to polarization of naive CD4(+) cells toward a non-pathogenic and/or regulatory phenotype.
Laroux
F Stephen
FS
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, 1501 Kings Highway, LA 71130, USA.
Norris
Hillary H
HH
Houghton
Jeff
J
Pavlick
Kevin P
KP
Bharwani
Sulaiman
S
Merrill
Dana M
DM
Fuseler
John
J
Chervenak
Robert
R
Grisham
Matthew B
MB
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*
D018398:Homeodomain Proteins; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens