Differential requirement for CD18 in T-helper effector homing

Seung Hyo Lee; Joseph E. Prince; Muhammad Rais; Farrah Kheradmand; Felix Shardonofsky; Huifang Lu; Arthur L. Beaudet; C. Wayne Smith; Lynn Soong; David Corry

doi:10.1038/nm932

Differential requirement for CD18 in T-helper effector homing

Seung Hyo Lee, Joseph E. Prince, Muhammad Rais, Farrah Kheradmand, Felix Shardonofsky, Huifang Lu, Arthur L. Beaudet, C. Wayne Smith, Lynn Soong, David Corry

Research Institute

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

To understand the integrin requirements of T-helper (T_H) effector subsets, we investigated the contribution of CD18 (β₂ integrin) to T_H1 and T_H2 function in vitro and in relevant disease models. CD18-deficient (Itgb2^-/-) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2 ^-/- mice were better able to resolve Leishmania major infection and generated a superior T_H1 immune response, as assessed from draining lymph nodes. In contrast, T_H2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of T_H1 and T_H2 cells in spleens was normal, but accumulation of T _H2 (not T_H1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for T_H2, but not T_H1, homing and has a minimal influence on T-effector development. These findings suggest a new integrin-based therapeutic approach in which the outcomes of diverse diseases may be favorably influenced by altering the homing of T _H2 cells.

Original language	English (US)
Pages (from-to)	1281-1286
Number of pages	6
Journal	Nature Medicine
Volume	9
Issue number	10
DOIs	https://doi.org/10.1038/nm932
State	Published - Oct 2003

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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title = "Differential requirement for CD18 in T-helper effector homing",

abstract = "To understand the integrin requirements of T-helper (TH) effector subsets, we investigated the contribution of CD18 (β2 integrin) to TH1 and TH2 function in vitro and in relevant disease models. CD18-deficient (Itgb2-/-) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2 -/- mice were better able to resolve Leishmania major infection and generated a superior TH1 immune response, as assessed from draining lymph nodes. In contrast, TH2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of TH1 and TH2 cells in spleens was normal, but accumulation of T H2 (not TH1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for TH2, but not TH1, homing and has a minimal influence on T-effector development. These findings suggest a new integrin-based therapeutic approach in which the outcomes of diverse diseases may be favorably influenced by altering the homing of T H2 cells.",

author = "Lee, {Seung Hyo} and Prince, {Joseph E.} and Muhammad Rais and Farrah Kheradmand and Felix Shardonofsky and Huifang Lu and Beaudet, {Arthur L.} and Smith, {C. Wayne} and Lynn Soong and David Corry",

note = "Funding Information: This work was supported by grants HL69585-01 (to D.B.C.), HL64061-01 (to F.K.) and F32-HL09657-02 (to H.L.) from the National Institutes of Health. We thank J. Xu and Y. Qian for technical assistance, and J.R. Rodgers, B.W. McIntyre and C.M. Ballantyne for helpful discussions.",

year = "2003",

month = oct,

doi = "10.1038/nm932",

language = "English (US)",

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T1 - Differential requirement for CD18 in T-helper effector homing

AU - Lee, Seung Hyo

AU - Prince, Joseph E.

AU - Rais, Muhammad

AU - Kheradmand, Farrah

AU - Shardonofsky, Felix

AU - Lu, Huifang

AU - Beaudet, Arthur L.

AU - Smith, C. Wayne

AU - Soong, Lynn

AU - Corry, David

N1 - Funding Information: This work was supported by grants HL69585-01 (to D.B.C.), HL64061-01 (to F.K.) and F32-HL09657-02 (to H.L.) from the National Institutes of Health. We thank J. Xu and Y. Qian for technical assistance, and J.R. Rodgers, B.W. McIntyre and C.M. Ballantyne for helpful discussions.

PY - 2003/10

Y1 - 2003/10

N2 - To understand the integrin requirements of T-helper (TH) effector subsets, we investigated the contribution of CD18 (β2 integrin) to TH1 and TH2 function in vitro and in relevant disease models. CD18-deficient (Itgb2-/-) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2 -/- mice were better able to resolve Leishmania major infection and generated a superior TH1 immune response, as assessed from draining lymph nodes. In contrast, TH2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of TH1 and TH2 cells in spleens was normal, but accumulation of T H2 (not TH1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for TH2, but not TH1, homing and has a minimal influence on T-effector development. These findings suggest a new integrin-based therapeutic approach in which the outcomes of diverse diseases may be favorably influenced by altering the homing of T H2 cells.

AB - To understand the integrin requirements of T-helper (TH) effector subsets, we investigated the contribution of CD18 (β2 integrin) to TH1 and TH2 function in vitro and in relevant disease models. CD18-deficient (Itgb2-/-) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2 -/- mice were better able to resolve Leishmania major infection and generated a superior TH1 immune response, as assessed from draining lymph nodes. In contrast, TH2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of TH1 and TH2 cells in spleens was normal, but accumulation of T H2 (not TH1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for TH2, but not TH1, homing and has a minimal influence on T-effector development. These findings suggest a new integrin-based therapeutic approach in which the outcomes of diverse diseases may be favorably influenced by altering the homing of T H2 cells.

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Differential requirement for CD18 in T-helper effector homing

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