CC chemokine receptor 9 expression defines a subset of peripheral blood lymphocytes with mucosal T cell phenotype and Th1 or T-regulatory 1 cytokine profile.
The chemokine receptor CCR9 is expressed on most small intestinal lamina propria and intraepithelial lymphocytes and on a small subset of peripheral blood lymphocytes. CCR9-expressing lymphocytes may play an important role in small bowel immunity and inflammation. We studied the phenotype and functional characteristics of CCR9(+) lymphocytes in blood from normal donors. A subset of CCR9(+) T cells have a phenotype of activated cells and constitutively express the costimulatory molecules CD40L and OX-40. In contrast to CCR9(-), CCR9(+)CD4(+) peripheral blood T cells proliferate to anti-CD3 or anti-CD2 stimulation and produce high levels of IFN-gamma and IL-10. IL-10-producing cells were exclusively detected within the CCR9(+) subset of CD4(+) T cells by intracellular staining and were distinct from IL-2- and IFN-gamma-producing cells. Moreover, memory CCR9(+)CD4(+) lymphocytes respond to CD2 stimulation with proliferation and IFN-gamma/IL-10 production, whereas memory CCR9(-)CD4(+) cells were unresponsive. In addition, memory CCR9(+)CD4(+) T cells support Ig production by cocultured CD19(+) B cells in the absence of prior T cell activation or addition of exogenous cytokines. Our data show that the memory subset of circulating CCR9(+)CD4(+) T cells has characteristics of mucosal T lymphocytes and contains cells with either Th1 or T-regulatory 1 cytokine profiles. Studies on the cytokine profile and Ag specificity of this cell subset could provide important insight into small intestinal immune-mediated diseases and oral tolerance in humans.
Papadakis
Konstantinos A
KA
Burns and Allen Research Institute and Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USA. Papadakis@cshs.org
Landers
Carol
C
Prehn
John
J
Kouroumalis
Elias A
EA
Moreno
Sofia T
ST
Gutierrez-Ramos
Jose-Carlos
JC
Hodge
Martin R
MR
Targan
Stephan R
SR
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002446:Celiac Disease / Q000276:immunology; D019742:Chemokines, CC / Q000378:metabolism; D018920:Coculture Techniques; D003424:Crohn Disease / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*
C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D016207:Cytokines; D007136:Immunoglobulins; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D016753:Interleukin-10