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 output: Contribution to journal › Article › peer-review

36 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

General Biochemistry, Genetics and Molecular Biology

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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",

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doi = "10.1038/nm932",

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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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