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

α4β7 and P-lig define three CD4+ memory T cell populations that differentially localize in intestinal and cutaneous lymphoid organs. (Left) CD4 and CD45RB expression by lymphocytes isolated from the cutaneous PLNs of a >1-y-old BALB/c mouse. The gates used to define ‘naive’ (CD4+CD45RB+) and ‘memory’ (CD4+CD45RB−) T cells are shown. (Right) α4β7 and P-lig expression by gated naive and memory CD4+ T cells isolated from the indicated lymphoid tissues of a >1-y-old BALB/c mouse.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196018&req=5

fig1: α4β7 and P-lig define three CD4+ memory T cell populations that differentially localize in intestinal and cutaneous lymphoid organs. (Left) CD4 and CD45RB expression by lymphocytes isolated from the cutaneous PLNs of a >1-y-old BALB/c mouse. The gates used to define ‘naive’ (CD4+CD45RB+) and ‘memory’ (CD4+CD45RB−) T cells are shown. (Right) α4β7 and P-lig expression by gated naive and memory CD4+ T cells isolated from the indicated lymphoid tissues of a >1-y-old BALB/c mouse.

Mentions: BALB/c and DO11.10xRAG2−/− mice were bred and housed at the Veterans Administration Hospital in Palo Alto, CA. Mice used in experiments shown in Figs. 1 and 2 were >1 y old. For all other experiments, mice were 1–3 mo old. BALB/c mice were given between 5–10 × 106 erythrocyte-depleted splenocytes from sex-matched DO11.10xRAG-2−/− animals by retroorbital injection 24 h before immunization. For 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeling, cells were incubated for 10 min at 37°C in HBSS (5 × 106 cells per milliliter) containing 500 nM CFSE (Molecular Probes).


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)

α4β7 and P-lig define three CD4+ memory T cell populations that differentially localize in intestinal and cutaneous lymphoid organs. (Left) CD4 and CD45RB expression by lymphocytes isolated from the cutaneous PLNs of a >1-y-old BALB/c mouse. The gates used to define ‘naive’ (CD4+CD45RB+) and ‘memory’ (CD4+CD45RB−) T cells are shown. (Right) α4β7 and P-lig expression by gated naive and memory CD4+ T cells isolated from the indicated lymphoid tissues of a >1-y-old BALB/c mouse.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: α4β7 and P-lig define three CD4+ memory T cell populations that differentially localize in intestinal and cutaneous lymphoid organs. (Left) CD4 and CD45RB expression by lymphocytes isolated from the cutaneous PLNs of a >1-y-old BALB/c mouse. The gates used to define ‘naive’ (CD4+CD45RB+) and ‘memory’ (CD4+CD45RB−) T cells are shown. (Right) α4β7 and P-lig expression by gated naive and memory CD4+ T cells isolated from the indicated lymphoid tissues of a >1-y-old BALB/c mouse.
Mentions: BALB/c and DO11.10xRAG2−/− mice were bred and housed at the Veterans Administration Hospital in Palo Alto, CA. Mice used in experiments shown in Figs. 1 and 2 were >1 y old. For all other experiments, mice were 1–3 mo old. BALB/c mice were given between 5–10 × 106 erythrocyte-depleted splenocytes from sex-matched DO11.10xRAG-2−/− animals by retroorbital injection 24 h before immunization. For 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeling, cells were incubated for 10 min at 37°C in HBSS (5 × 106 cells per milliliter) containing 500 nM CFSE (Molecular Probes).

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