Studies on the Mechanisms by which Transforming Growth Factor-β (TGF-β) Protects against Allergic Encephalomyelitis: Antagonism between TGF-β and Tumor Necrosis Factor

Laura Santambrogio, Gerald M. Hochwald, Babita Saxena, Chin Hung Leu, Joseph E. Martz, Joseph A. Carlino, Nancy H. Ruddle, Michael A. Palladino, Leslie I. Gold, G. Jeanette Thorbecke

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease in which peripheral lymphoid cells are activated by immunization with myelin proteins and become effector cells that traverse the central nervous system (CNS) capillaries and initiate inflammatory demyelinating lesions. The administration of transforming growth factor-β (TGF-β) has been shown previously to decrease the incidence and severity of EAE. In our studies we have determined: 1) the effects of TGF-β injected at different intervals after the EAE-inducing immunization; 2) the effect of TGF-β on the development of sensitized T cells, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood; 3) the extent of lymphoid cell infiltration in CNS of TGF-β-treated and control mice; and 4) the role of endogenous TGF-β and TNF in determining the severity of both acute and relapsing EAE. The onset of acute-EAE in SJL mice, induced by immunization with spinal cord homogenate in CFA and pertussigen, is on days 10 to 15. Although daily i.p. injections of 0.2 to 2 ug TGF-β1, or TGF-β2 on days 5 to 9 after immunization are highly protective, injections on days 1 to 5 or 9 to 13 are not. Moreover, anti-TGF-β accelerates and aggravates EAE when given on days 5 and 9, but not on day 12. Anti-TNF, injected on days 5 and 9, provides a comparable degree of protection as does TGF-β. Similarly, in relapsing EAE, anti-TGF-β increases, whereas anti-TNF decreases the incidence and severity of relapses. TGF-β treatment on days 5 to 9 does not influence the appearance of sensitized cells in peripheral blood and lymph nodes, but does prevent the accumulation of T cells in brain and spinal cord, as assayed on days 15 to 20. It is concluded that the protective effect of TGF-β is exerted at the level of the target organ, CNS and/or its vascular endothelium, rather than through a direct effect on lymphoid cells, and that there is a small window of 4 days in which TGF-β exerts its protective effect.

Original languageEnglish (US)
Pages (from-to)1116-1127
Number of pages12
JournalJournal of Immunology
Volume151
Issue number2
StatePublished - Jul 15 1993
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Transforming Growth Factors
Tumor Necrosis Factor-alpha
Immunization
Central Nervous System
Lymphocytes
T-Lymphocytes
Spinal Cord
Lymph Nodes
Myelin Proteins
Injections
Incidence
Pertussis Toxin
Vascular Endothelium
Autoimmune Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

Santambrogio, L., Hochwald, G. M., Saxena, B., Leu, C. H., Martz, J. E., Carlino, J. A., ... Thorbecke, G. J. (1993). Studies on the Mechanisms by which Transforming Growth Factor-β (TGF-β) Protects against Allergic Encephalomyelitis: Antagonism between TGF-β and Tumor Necrosis Factor. Journal of Immunology, 151(2), 1116-1127.

Studies on the Mechanisms by which Transforming Growth Factor-β (TGF-β) Protects against Allergic Encephalomyelitis : Antagonism between TGF-β and Tumor Necrosis Factor. / Santambrogio, Laura; Hochwald, Gerald M.; Saxena, Babita; Leu, Chin Hung; Martz, Joseph E.; Carlino, Joseph A.; Ruddle, Nancy H.; Palladino, Michael A.; Gold, Leslie I.; Thorbecke, G. Jeanette.

In: Journal of Immunology, Vol. 151, No. 2, 15.07.1993, p. 1116-1127.

Research output: Contribution to journalArticle

Santambrogio, L, Hochwald, GM, Saxena, B, Leu, CH, Martz, JE, Carlino, JA, Ruddle, NH, Palladino, MA, Gold, LI & Thorbecke, GJ 1993, 'Studies on the Mechanisms by which Transforming Growth Factor-β (TGF-β) Protects against Allergic Encephalomyelitis: Antagonism between TGF-β and Tumor Necrosis Factor', Journal of Immunology, vol. 151, no. 2, pp. 1116-1127.
Santambrogio, Laura ; Hochwald, Gerald M. ; Saxena, Babita ; Leu, Chin Hung ; Martz, Joseph E. ; Carlino, Joseph A. ; Ruddle, Nancy H. ; Palladino, Michael A. ; Gold, Leslie I. ; Thorbecke, G. Jeanette. / Studies on the Mechanisms by which Transforming Growth Factor-β (TGF-β) Protects against Allergic Encephalomyelitis : Antagonism between TGF-β and Tumor Necrosis Factor. In: Journal of Immunology. 1993 ; Vol. 151, No. 2. pp. 1116-1127.
@article{4a779c5e268e46d582dbcb782b1ea739,
title = "Studies on the Mechanisms by which Transforming Growth Factor-β (TGF-β) Protects against Allergic Encephalomyelitis: Antagonism between TGF-β and Tumor Necrosis Factor",
abstract = "Experimental allergic encephalomyelitis (EAE) is an autoimmune disease in which peripheral lymphoid cells are activated by immunization with myelin proteins and become effector cells that traverse the central nervous system (CNS) capillaries and initiate inflammatory demyelinating lesions. The administration of transforming growth factor-β (TGF-β) has been shown previously to decrease the incidence and severity of EAE. In our studies we have determined: 1) the effects of TGF-β injected at different intervals after the EAE-inducing immunization; 2) the effect of TGF-β on the development of sensitized T cells, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood; 3) the extent of lymphoid cell infiltration in CNS of TGF-β-treated and control mice; and 4) the role of endogenous TGF-β and TNF in determining the severity of both acute and relapsing EAE. The onset of acute-EAE in SJL mice, induced by immunization with spinal cord homogenate in CFA and pertussigen, is on days 10 to 15. Although daily i.p. injections of 0.2 to 2 ug TGF-β1, or TGF-β2 on days 5 to 9 after immunization are highly protective, injections on days 1 to 5 or 9 to 13 are not. Moreover, anti-TGF-β accelerates and aggravates EAE when given on days 5 and 9, but not on day 12. Anti-TNF, injected on days 5 and 9, provides a comparable degree of protection as does TGF-β. Similarly, in relapsing EAE, anti-TGF-β increases, whereas anti-TNF decreases the incidence and severity of relapses. TGF-β treatment on days 5 to 9 does not influence the appearance of sensitized cells in peripheral blood and lymph nodes, but does prevent the accumulation of T cells in brain and spinal cord, as assayed on days 15 to 20. It is concluded that the protective effect of TGF-β is exerted at the level of the target organ, CNS and/or its vascular endothelium, rather than through a direct effect on lymphoid cells, and that there is a small window of 4 days in which TGF-β exerts its protective effect.",
author = "Laura Santambrogio and Hochwald, {Gerald M.} and Babita Saxena and Leu, {Chin Hung} and Martz, {Joseph E.} and Carlino, {Joseph A.} and Ruddle, {Nancy H.} and Palladino, {Michael A.} and Gold, {Leslie I.} and Thorbecke, {G. Jeanette}",
year = "1993",
month = "7",
day = "15",
language = "English (US)",
volume = "151",
pages = "1116--1127",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Studies on the Mechanisms by which Transforming Growth Factor-β (TGF-β) Protects against Allergic Encephalomyelitis

T2 - Antagonism between TGF-β and Tumor Necrosis Factor

AU - Santambrogio, Laura

AU - Hochwald, Gerald M.

AU - Saxena, Babita

AU - Leu, Chin Hung

AU - Martz, Joseph E.

AU - Carlino, Joseph A.

AU - Ruddle, Nancy H.

AU - Palladino, Michael A.

AU - Gold, Leslie I.

AU - Thorbecke, G. Jeanette

PY - 1993/7/15

Y1 - 1993/7/15

N2 - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease in which peripheral lymphoid cells are activated by immunization with myelin proteins and become effector cells that traverse the central nervous system (CNS) capillaries and initiate inflammatory demyelinating lesions. The administration of transforming growth factor-β (TGF-β) has been shown previously to decrease the incidence and severity of EAE. In our studies we have determined: 1) the effects of TGF-β injected at different intervals after the EAE-inducing immunization; 2) the effect of TGF-β on the development of sensitized T cells, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood; 3) the extent of lymphoid cell infiltration in CNS of TGF-β-treated and control mice; and 4) the role of endogenous TGF-β and TNF in determining the severity of both acute and relapsing EAE. The onset of acute-EAE in SJL mice, induced by immunization with spinal cord homogenate in CFA and pertussigen, is on days 10 to 15. Although daily i.p. injections of 0.2 to 2 ug TGF-β1, or TGF-β2 on days 5 to 9 after immunization are highly protective, injections on days 1 to 5 or 9 to 13 are not. Moreover, anti-TGF-β accelerates and aggravates EAE when given on days 5 and 9, but not on day 12. Anti-TNF, injected on days 5 and 9, provides a comparable degree of protection as does TGF-β. Similarly, in relapsing EAE, anti-TGF-β increases, whereas anti-TNF decreases the incidence and severity of relapses. TGF-β treatment on days 5 to 9 does not influence the appearance of sensitized cells in peripheral blood and lymph nodes, but does prevent the accumulation of T cells in brain and spinal cord, as assayed on days 15 to 20. It is concluded that the protective effect of TGF-β is exerted at the level of the target organ, CNS and/or its vascular endothelium, rather than through a direct effect on lymphoid cells, and that there is a small window of 4 days in which TGF-β exerts its protective effect.

AB - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease in which peripheral lymphoid cells are activated by immunization with myelin proteins and become effector cells that traverse the central nervous system (CNS) capillaries and initiate inflammatory demyelinating lesions. The administration of transforming growth factor-β (TGF-β) has been shown previously to decrease the incidence and severity of EAE. In our studies we have determined: 1) the effects of TGF-β injected at different intervals after the EAE-inducing immunization; 2) the effect of TGF-β on the development of sensitized T cells, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood; 3) the extent of lymphoid cell infiltration in CNS of TGF-β-treated and control mice; and 4) the role of endogenous TGF-β and TNF in determining the severity of both acute and relapsing EAE. The onset of acute-EAE in SJL mice, induced by immunization with spinal cord homogenate in CFA and pertussigen, is on days 10 to 15. Although daily i.p. injections of 0.2 to 2 ug TGF-β1, or TGF-β2 on days 5 to 9 after immunization are highly protective, injections on days 1 to 5 or 9 to 13 are not. Moreover, anti-TGF-β accelerates and aggravates EAE when given on days 5 and 9, but not on day 12. Anti-TNF, injected on days 5 and 9, provides a comparable degree of protection as does TGF-β. Similarly, in relapsing EAE, anti-TGF-β increases, whereas anti-TNF decreases the incidence and severity of relapses. TGF-β treatment on days 5 to 9 does not influence the appearance of sensitized cells in peripheral blood and lymph nodes, but does prevent the accumulation of T cells in brain and spinal cord, as assayed on days 15 to 20. It is concluded that the protective effect of TGF-β is exerted at the level of the target organ, CNS and/or its vascular endothelium, rather than through a direct effect on lymphoid cells, and that there is a small window of 4 days in which TGF-β exerts its protective effect.

UR - http://www.scopus.com/inward/record.url?scp=0027313082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027313082&partnerID=8YFLogxK

M3 - Article

C2 - 8335893

AN - SCOPUS:0027313082

VL - 151

SP - 1116

EP - 1127

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -