IFN-gamma-inducible chemokines enhance adaptive immunity and colitis.
T helper type 1 (Th1) cells secreting interferon-gamma (IFN-gamma) have been closely associated with Crohn's disease (CD). Monokine-induced by IFN-gamma (MIG), IFN-gamma-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10), are chemokines that bind CXCR3 and mediate the chemotaxis of leukocytes. IP-10, MIG, and CXCR3 have been shown to be expressed at sites of CD. The current study stems from our recent findings that IP-10, MIG, and I-TAC significantly contribute to the development of Th1-mediated inflammatory responses. To better understand the role of CXCR3 interactions during CD, we characterized the effects of IP-10, MIG, I-TAC, and CXCR3+ T cells on mucosal immune responses. IP-10, MIG, and I-TAC significantly enhanced antigen-specific serum and mucosal antibodies through Th1-mediated events and CD28 modulation. Additionally, the adoptive transfer of naive CXCR3+ T cells and CD4+CD45RB(HI) to T cell receptor beta (TCRbeta) x delta(-/-) mice resulted in the onset of murine colitis. Taken together, these studies suggest that IP-10, MIG, I-TAC, and CXCR3 interactions are involved in mucosal immune responses required for the induction of CD.
Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Udai P
UP
Singh
Shailesh
S
Singh
Nuzhat
N
Iqbal
Casey T
CT
Weaver
Jerry R
JR
McGhee
James W
JW
Lillard
D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D000918:Antibody Specificity; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D018925:Chemokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency / Q000235:genetics; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018106:CD28 Antigens; D018925:Chemokines; C515188:Cxcr3 protein, mouse; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D010047:Ovalbumin