Limits...
Rapid acquisition of tissue-specific homing phenotypes by CD4(+) T cells activated in cutaneous or mucosal lymphoid tissues.

Campbell DJ, Butcher EC - J. Exp. Med. (2002)

Bottom Line: However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattractant receptors targeting them to the corresponding nonlymphoid site.We define two murine CD4(+) effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and alpha 4 beta 7, respectively.Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. daniel@macampbell.com

ABSTRACT
Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of 'tissue-specific' adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattractant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4(+) effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and alpha 4 beta 7, respectively. We show that within 2 d of systemic immunization CD4(+) T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate alpha 4 beta 7, while those responding to antigen in intestinal lymph nodes selectively express high levels of alpha 4 beta 7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

Show MeSH

Related in: MedlinePlus

CD4+ T cells activated in PLNs or MLNs differentially respond to the intestinal chemokine TECK. Migration of CD4+KJ1–26+ cells isolated from the MLNs or PLNs 2 d after intraperitoneal immunization of DO11.10 adoptive transfer recipients with OVA plus LPS to medium alone (white bars) or to the indicated chemokines (gray bars). Data are mean and SD of multiple measurements taken in one experiment, which is representative of 4.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196018&req=5

fig4: CD4+ T cells activated in PLNs or MLNs differentially respond to the intestinal chemokine TECK. Migration of CD4+KJ1–26+ cells isolated from the MLNs or PLNs 2 d after intraperitoneal immunization of DO11.10 adoptive transfer recipients with OVA plus LPS to medium alone (white bars) or to the indicated chemokines (gray bars). Data are mean and SD of multiple measurements taken in one experiment, which is representative of 4.

Mentions: Chemokines are also thought to contribute to tissue-specific lymphocyte homing. Outside of the thymus, the chemokine TECK is expressed selectively by epithelial cells of the small intestine, where it is believed to participate in the homing or retention of lymphocytes in the ILP and intestinal epithelium (6). Accordingly, a subset of circulating α4β7hi memory T cells and nearly all lymphocytes isolated from the ILP and intestinal epithelium of human jejunum express the TECK receptor CCR9 (5, 6). Therefore, we examined the TECK responsiveness of antigen-specific T cells activated in the MLNs or PLNs 2 d after systemic OVA immunization. In parallel with their specific expression of α4β7, only the cells activated in the MLNs migrated to TECK in this assay, whereas cells activated in both locations responded to the chemokine IP-10, which is broadly expressed at many inflammatory sites (reference 16; Fig. 4) . Thus, naive CD4+ T cell activation in cutaneous or intestinal lymphoid tissues results in the rapid induction or selection of effector cells displaying patterns of adhesion and chemoattractant receptors expected to target them to inflamed skin or the ILP, respectively.


Rapid acquisition of tissue-specific homing phenotypes by CD4(+) T cells activated in cutaneous or mucosal lymphoid tissues.

Campbell DJ, Butcher EC - J. Exp. Med. (2002)

CD4+ T cells activated in PLNs or MLNs differentially respond to the intestinal chemokine TECK. Migration of CD4+KJ1–26+ cells isolated from the MLNs or PLNs 2 d after intraperitoneal immunization of DO11.10 adoptive transfer recipients with OVA plus LPS to medium alone (white bars) or to the indicated chemokines (gray bars). Data are mean and SD of multiple measurements taken in one experiment, which is representative of 4.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196018&req=5

fig4: CD4+ T cells activated in PLNs or MLNs differentially respond to the intestinal chemokine TECK. Migration of CD4+KJ1–26+ cells isolated from the MLNs or PLNs 2 d after intraperitoneal immunization of DO11.10 adoptive transfer recipients with OVA plus LPS to medium alone (white bars) or to the indicated chemokines (gray bars). Data are mean and SD of multiple measurements taken in one experiment, which is representative of 4.
Mentions: Chemokines are also thought to contribute to tissue-specific lymphocyte homing. Outside of the thymus, the chemokine TECK is expressed selectively by epithelial cells of the small intestine, where it is believed to participate in the homing or retention of lymphocytes in the ILP and intestinal epithelium (6). Accordingly, a subset of circulating α4β7hi memory T cells and nearly all lymphocytes isolated from the ILP and intestinal epithelium of human jejunum express the TECK receptor CCR9 (5, 6). Therefore, we examined the TECK responsiveness of antigen-specific T cells activated in the MLNs or PLNs 2 d after systemic OVA immunization. In parallel with their specific expression of α4β7, only the cells activated in the MLNs migrated to TECK in this assay, whereas cells activated in both locations responded to the chemokine IP-10, which is broadly expressed at many inflammatory sites (reference 16; Fig. 4) . Thus, naive CD4+ T cell activation in cutaneous or intestinal lymphoid tissues results in the rapid induction or selection of effector cells displaying patterns of adhesion and chemoattractant receptors expected to target them to inflamed skin or the ILP, respectively.

Bottom Line: However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattractant receptors targeting them to the corresponding nonlymphoid site.We define two murine CD4(+) effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and alpha 4 beta 7, respectively.Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. daniel@macampbell.com

ABSTRACT
Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of 'tissue-specific' adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattractant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4(+) effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and alpha 4 beta 7, respectively. We show that within 2 d of systemic immunization CD4(+) T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate alpha 4 beta 7, while those responding to antigen in intestinal lymph nodes selectively express high levels of alpha 4 beta 7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

Show MeSH
Related in: MedlinePlus