Acquisition of selectin binding and peripheral homing properties by CD4(+) and CD8(+) T cells.
Different T cell subsets exhibit distinct capacities to migrate into peripheral sites of inflammation, and this may in part reflect differential expression of homing receptors and chemokine receptors. Using an adoptive transfer approach, we examined the ability of functionally distinct subsets of T cells to home to a peripheral inflammatory site. The data directly demonstrate the inability of naive T cells and the ability of effector cells to home to inflamed peritoneum. Furthermore, interleukin (IL)-12 directs the differentiation of either CD4(+) or CD8(+) T cells into effector populations that expresses functional E- and P-selectin ligand and that are preferentially recruited into the inflamed peritoneum compared with T cells differentiated in the presence of IL-4. Recruitment can be blocked by anti-E- and -P-selectin antibodies. The presence of antigen in the peritoneum promotes local proliferation of recruited T cells, and significantly amplifies the Th1 polarization of the lymphocytic infiltrate. Preferential recruitment of Th1 cells into the peritoneum is also seen when cytokine response gene 2 (CRG-2)/interferon gamma-inducible protein 10 (IP-10) is used as the sole inflammatory stimulus. We have also found that P-selectin binds only to antigen-specific T cells in draining lymph nodes after immunization, implying that both antigen- and cytokine-mediated signals are required for expression of functional selectin-ligand.
Xie
H
H
Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Lim
Y C
YC
Luscinskas
F W
FW
Lichtman
A H
AH
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000008:administration & dosage; D019040:E-Selectin / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000008:administration & dosage; D019007:P-Selectin / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D019087:Selectins / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; D019040:E-Selectin; D015846:Monokines; D019007:P-Selectin; D016201:Receptors, Lymphocyte Homing; D019087:Selectins; D018664:Interleukin-12; D015847:Interleukin-4