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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.

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P-lig expression does not distinguish Th1, Th2, and Th0 cells analyzed directly ex vivo. (A, top) IFN-γ and IL-4 expression by gated CD4+ T cells determined by intracellular cytokine staining and flow cytometry after 4 h of PMA plus ionomycin stimulation of lymphocytes isolated from the indicated organs. (Bottom) Staining of stimulated lymphocytes from PLNs with isotype control antibodies. (B) Percentage of P-lig+ cells among gated Th1, Th2, and Th0 CD4+ T cells isolated from the indicated organs. Each data point represents a measurement taken from an individual animal. A total of three >1-y-old BALB/c mice were analyzed.
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fig2: P-lig expression does not distinguish Th1, Th2, and Th0 cells analyzed directly ex vivo. (A, top) IFN-γ and IL-4 expression by gated CD4+ T cells determined by intracellular cytokine staining and flow cytometry after 4 h of PMA plus ionomycin stimulation of lymphocytes isolated from the indicated organs. (Bottom) Staining of stimulated lymphocytes from PLNs with isotype control antibodies. (B) Percentage of P-lig+ cells among gated Th1, Th2, and Th0 CD4+ T cells isolated from the indicated organs. Each data point represents a measurement taken from an individual animal. A total of three >1-y-old BALB/c mice were analyzed.

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)

P-lig expression does not distinguish Th1, Th2, and Th0 cells analyzed directly ex vivo. (A, top) IFN-γ and IL-4 expression by gated CD4+ T cells determined by intracellular cytokine staining and flow cytometry after 4 h of PMA plus ionomycin stimulation of lymphocytes isolated from the indicated organs. (Bottom) Staining of stimulated lymphocytes from PLNs with isotype control antibodies. (B) Percentage of P-lig+ cells among gated Th1, Th2, and Th0 CD4+ T cells isolated from the indicated organs. Each data point represents a measurement taken from an individual animal. A total of three >1-y-old BALB/c mice were analyzed.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: P-lig expression does not distinguish Th1, Th2, and Th0 cells analyzed directly ex vivo. (A, top) IFN-γ and IL-4 expression by gated CD4+ T cells determined by intracellular cytokine staining and flow cytometry after 4 h of PMA plus ionomycin stimulation of lymphocytes isolated from the indicated organs. (Bottom) Staining of stimulated lymphocytes from PLNs with isotype control antibodies. (B) Percentage of P-lig+ cells among gated Th1, Th2, and Th0 CD4+ T cells isolated from the indicated organs. Each data point represents a measurement taken from an individual animal. A total of three >1-y-old BALB/c mice were analyzed.
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