Abstract
To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1-/-) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naïve immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4+BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4-CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R-recipients, thus implicating differing mechanisms of protection.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 89-103 |
| Number of pages | 15 |
| Journal | Journal of Neuroscience Research |
| Volume | 71 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2003 |
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Keywords
- CD4+ T cells
- EAE
- Regulatory T cells
- TCR transgenic mice
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Endogenous CD4+BV8S2- T cells from TG BV8S2+ donors confer complete protection against spontaneous experimental encephalomyelitis (Sp-EAE) in TCR transgenic, RAG-/- mice. / Matejuk, Agata; Buenafe, Abigail C.; Dwyer, Jami; Ito, Atsushi; Silverman, Marc; Zamora, Alex; Subramanian, Sandhya; Vandenbark, Arthur; Offner, Halina.
In: Journal of Neuroscience Research, Vol. 71, No. 1, 01.01.2003, p. 89-103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endogenous CD4+BV8S2- T cells from TG BV8S2+ donors confer complete protection against spontaneous experimental encephalomyelitis (Sp-EAE) in TCR transgenic, RAG-/- mice
AU - Matejuk, Agata
AU - Buenafe, Abigail C.
AU - Dwyer, Jami
AU - Ito, Atsushi
AU - Silverman, Marc
AU - Zamora, Alex
AU - Subramanian, Sandhya
AU - Vandenbark, Arthur
AU - Offner, Halina
PY - 2003/1/1
Y1 - 2003/1/1
N2 - To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1-/-) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naïve immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4+BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4-CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R-recipients, thus implicating differing mechanisms of protection.
AB - To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1-/-) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naïve immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4+BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4-CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R-recipients, thus implicating differing mechanisms of protection.
KW - CD4+ T cells
KW - EAE
KW - Regulatory T cells
KW - TCR transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=0037214470&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037214470&partnerID=8YFLogxK
U2 - 10.1002/jnr.10450
DO - 10.1002/jnr.10450
M3 - Article
C2 - 12478617
AN - SCOPUS:0037214470
VL - 71
SP - 89
EP - 103
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 1
ER -