Abstract
Ptpn22 is one of the most potent autoimmunity predisposing genes and strongly associates with type 1 diabetes (T1D). Previous studies showed that non-obese diabetic mice with reduced expression levels of Ptpn22 are protected from T1D due to increased number of T regulatory (Treg) cells. We report that lack of Ptpn22 exacerbates virally-induced T1D in female rat insulin promoter lymphocytic choriomeningitis virus (RIP-LCMV-GP) mice, while maintaining higher number of Treg cells throughout the antiviral response in the blood and spleen but not in the pancreatic lymph nodes. GP33-41-specific pentamer-positive cytotoxic lymphocytes (CTLs) are numerically reduced in the absence of Ptpn22 at the expansion and contraction phase but reach wild-type levels at the memory phase. However, they show similar effector function and even a subtle increase in the production of IL-2. In contrast, NP396-404-specific CTLs develop normally at all phases but display enhanced effector function. Lack of Ptpn22 also augments the memory proinflammatory response of GP61-80 CD4 T cells. Hence, lack of Ptpn22 largely augments antiviral effector T cell responses, suggesting that caution should be taken when targeting Ptpn22 to treat autoimmune diseases where viral infections are considered environmental triggers.
| Original language | English |
|---|---|
| Pages (from-to) | 98-108 |
| Number of pages | 11 |
| Journal | Clinical Immunology |
| Volume | 156 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2015 |
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Keywords
- Cytotoxic lymphocytes (CTLs);
- Memory CD8<sup>+</sup> T cells;
- Ptpn22;
- Treg cells
- Type 1 diabetes (T1D);
- Virally-induced T1D;
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
PTPN22 controls virally-induced autoimmune diabetes by modulating cytotoxic T lymphocyte responses in an epitope-specific manner. / Fousteri, Georgia; Jofra, Tatiana; Di Fonte, Roberta; Kuka, Mirela; Iannacone, Matteo; Battaglia, Manuela.
In: Clinical Immunology, Vol. 156, No. 2, 01.02.2015, p. 98-108.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PTPN22 controls virally-induced autoimmune diabetes by modulating cytotoxic T lymphocyte responses in an epitope-specific manner
AU - Fousteri, Georgia
AU - Jofra, Tatiana
AU - Di Fonte, Roberta
AU - Kuka, Mirela
AU - Iannacone, Matteo
AU - Battaglia, Manuela
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Ptpn22 is one of the most potent autoimmunity predisposing genes and strongly associates with type 1 diabetes (T1D). Previous studies showed that non-obese diabetic mice with reduced expression levels of Ptpn22 are protected from T1D due to increased number of T regulatory (Treg) cells. We report that lack of Ptpn22 exacerbates virally-induced T1D in female rat insulin promoter lymphocytic choriomeningitis virus (RIP-LCMV-GP) mice, while maintaining higher number of Treg cells throughout the antiviral response in the blood and spleen but not in the pancreatic lymph nodes. GP33-41-specific pentamer-positive cytotoxic lymphocytes (CTLs) are numerically reduced in the absence of Ptpn22 at the expansion and contraction phase but reach wild-type levels at the memory phase. However, they show similar effector function and even a subtle increase in the production of IL-2. In contrast, NP396-404-specific CTLs develop normally at all phases but display enhanced effector function. Lack of Ptpn22 also augments the memory proinflammatory response of GP61-80 CD4 T cells. Hence, lack of Ptpn22 largely augments antiviral effector T cell responses, suggesting that caution should be taken when targeting Ptpn22 to treat autoimmune diseases where viral infections are considered environmental triggers.
AB - Ptpn22 is one of the most potent autoimmunity predisposing genes and strongly associates with type 1 diabetes (T1D). Previous studies showed that non-obese diabetic mice with reduced expression levels of Ptpn22 are protected from T1D due to increased number of T regulatory (Treg) cells. We report that lack of Ptpn22 exacerbates virally-induced T1D in female rat insulin promoter lymphocytic choriomeningitis virus (RIP-LCMV-GP) mice, while maintaining higher number of Treg cells throughout the antiviral response in the blood and spleen but not in the pancreatic lymph nodes. GP33-41-specific pentamer-positive cytotoxic lymphocytes (CTLs) are numerically reduced in the absence of Ptpn22 at the expansion and contraction phase but reach wild-type levels at the memory phase. However, they show similar effector function and even a subtle increase in the production of IL-2. In contrast, NP396-404-specific CTLs develop normally at all phases but display enhanced effector function. Lack of Ptpn22 also augments the memory proinflammatory response of GP61-80 CD4 T cells. Hence, lack of Ptpn22 largely augments antiviral effector T cell responses, suggesting that caution should be taken when targeting Ptpn22 to treat autoimmune diseases where viral infections are considered environmental triggers.
KW - Cytotoxic lymphocytes (CTLs);
KW - Memory CD8<sup>+</sup> T cells;
KW - Ptpn22;
KW - Treg cells
KW - Type 1 diabetes (T1D);
KW - Virally-induced T1D;
UR - http://www.scopus.com/inward/record.url?scp=84919934960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919934960&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2014.12.002
DO - 10.1016/j.clim.2014.12.002
M3 - Article
C2 - 25513733
AN - SCOPUS:84919934960
VL - 156
SP - 98
EP - 108
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
IS - 2
ER -