The Role of the Thymus in the Control of Autoimmunity

Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell anergy or T cell indifference for those whose expression is solely extra-thymic. These mechanisms are passive in that they depend on autoreactiv...

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Veröffentlicht in:Journal of autoimmunity Jg. 9; H. 2; S. 241 - 246
Hauptverfasser: Heath, Victoria L., Saoudi, Abdelhadi, Seddon, Benedict P., Moore, Nel C., Fowell, Deborah J., Mason, Don W.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Elsevier Ltd 01.04.1996
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ISSN:0896-8411, 1095-9157
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Abstract Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell anergy or T cell indifference for those whose expression is solely extra-thymic. These mechanisms are passive in that they depend on autoreactive T cells being either eliminated during their maturation or rendered intrinsically non-responsive after they have matured. The data presented in this paper indicate that this scheme requires modification. First, it is evident that self antigens that are commonly regarded as being tissue-specific may also be expressed in the thymus where they influence the developing T cell repertoire. Second, it appears that there is some T cell-mediated regulatory mechanism that actively prevents potentially autoreactive T cells from expressing their disease-inducing potential. Our data indicate that this regulatory mechanism is established intrathymically and is an innate property of the naive T cell repertoire. The mechanism is discussed in terms of what is currently known of the ways that an individual T cell responds when interacting with agonist and antagonist peptides and possible therapeutic implications are considered.
AbstractList Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell anergy or T cell indifference for those whose expression is solely extra-thymic. These mechanisms are passive in that they depend on autoreactive T cells being either eliminated during their maturation or rendered intrinsically non-responsive after they have matured. The data presented in this paper indicate that this scheme requires modification. First, it is evident that self antigens that are commonly regarded as being tissue-specific may also be expressed in the thymus where they influence the developing T cell repertoire. Second, it appears that there is some T cell-mediated regulatory mechanism that actively prevents potentially autoreactive T cells from expressing their disease-inducing potential. Our data indicate that this regulatory mechanism is established intrathymically and is an innate property of the naive T cell repertoire. The mechanism is discussed in terms of what is currently known of the ways that an individual T cell responds when interacting with agonist and antagonist peptides and possible therapeutic implications are considered.
Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell anergy or T cell indifference for those whose expression is solely extrathymic. These mechanisms are passive in that they depend on autoreactive T cells being either eliminated during their maturation or rendered intrinsically non-responsive after they have matured. The data presented in this paper indicate that this scheme requires modification. First, it is evident that self antigens that are commonly regarded as being tissue-specific may also be expressed in the thymus where they influence the developing T cell repertoire. Second, it appears that there is some T cell-mediated regulatory mechanism that actively prevents potentially autoreactive T cells from expressing their disease-inducing potential. Our data indicate that this regulatory mechanism is established intrathymically and is an innate property of the naive T cell repertoire. The mechanism is discussed in terms of what is currently known of the ways that an individual T cell responds when interacting with agonist and antagonist peptides and possible therapeutic implications are considered.
Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell anergy or T cell indifference for those whose expression is solely extrathymic. These mechanisms are passive in that they depend on autoreactive T cells being either eliminated during their maturation or rendered intrinsically non-responsive after they have matured. The data presented in this paper indicate that this scheme requires modification. First, it is evident that self antigens that are commonly regarded as being tissue-specific may also be expressed in the thymus where they influence the developing T cell repertoire. Second, it appears that there is some T cell-mediated regulatory mechanism that actively prevents potentially autoreactive T cells from expressing their disease-inducing potential. Our data indicate that this regulatory mechanism is established intrathymically and is an innate property of the naive T cell repertoire. The mechanism is discussed in terms of what is currently known of the ways that an individual T cell responds when interacting with agonist and antagonist peptides and possible therapeutic implications are considered.Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell anergy or T cell indifference for those whose expression is solely extrathymic. These mechanisms are passive in that they depend on autoreactive T cells being either eliminated during their maturation or rendered intrinsically non-responsive after they have matured. The data presented in this paper indicate that this scheme requires modification. First, it is evident that self antigens that are commonly regarded as being tissue-specific may also be expressed in the thymus where they influence the developing T cell repertoire. Second, it appears that there is some T cell-mediated regulatory mechanism that actively prevents potentially autoreactive T cells from expressing their disease-inducing potential. Our data indicate that this regulatory mechanism is established intrathymically and is an innate property of the naive T cell repertoire. The mechanism is discussed in terms of what is currently known of the ways that an individual T cell responds when interacting with agonist and antagonist peptides and possible therapeutic implications are considered.
Author Moore, Nel C.
Heath, Victoria L.
Saoudi, Abdelhadi
Seddon, Benedict P.
Fowell, Deborah J.
Mason, Don W.
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Issue 2
Keywords T cell anergy
self antigens
thymus
self tolerance
T cell indifference
Language English
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Snippet Self tolerance among T cells is believed to be maintained by two principal mechanisms: clonal deletion for self antigens expressed in the thymus and T cell...
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SubjectTerms Animals
Autoantigens - immunology
Autoimmune Diseases - immunology
Autoimmunity - immunology
Clonal Deletion
Diabetes Mellitus, Experimental - immunology
Humans
Rats
self antigens
self tolerance
Self Tolerance - immunology
T cell anergy
T cell indifference
T-Lymphocytes - immunology
thymus
Thymus Gland - immunology
Title The Role of the Thymus in the Control of Autoimmunity
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