Article

Paradoxical arrest in lupus activity in BXSB mice with highly autoreactive T cells.

Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.
Lupus (impact factor: 2.34). 11/2009; 19(2):182-91. DOI:10.1177/0961203309350756 pp.182-91
Source: PubMed

ABSTRACT T cells with high avidity for antigens are thought to mediate more effective immunity against foreign antigens and cause more severe autoimmunity. The impact of T cell receptor (TCR) avidity on the development of lupus has not been investigated. We took advantage of a transgenic mouse strain (designated MTB) that has a diverse T cell population and a globally stronger reactivity to self. [MTBxBXSB]F1 mice displayed accelerated lupus relative to the [WTxBXSB]F1 controls. The severity of lupus and the activation of T cells subsided with aging, when elevated IL-10 production by Tr1 cells was observed. Thus, chronic high avidity interactions of T cells with self-antigens can lead to an age associated increase in IL-10 production. This could explain the age-associated reduction of the incidence of lupus, as well as other autoimmune diseases. Furthermore, the principle of Tr1 differentiation based on diverse T cells with high avidity for self may potentially be used as a therapeutic strategy in the treatment of lupus.

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    Article: Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells.
    Zohreh Tatari-Calderone, Milica Stojakovic, Ramita Dewan, Gama Le Bouder, Dragana Jankovic, Stanislav Vukmanovic
    [show abstract] [hide abstract]
    ABSTRACT: Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases. The phenotype of T cells from aged mice (18-24 months) indicating functional TCR avidity (CD3 and CD5 expression) correlates with the level of preserved thymic function. In mice with moderate thymic output (> 30% of peripheral CD62L(hi) T cells), T cells displayed CD3(low)CD5(hi) phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62L(hi) T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3(low)CD5(hi) phenotype, followed by a CD3(low)CD5(low) phenotype. Spleens of old mice with the CD3(low)/CD5(hi) T cell phenotype displayed increased levels of IL-10 mRNA, and their T cells could be induced to secrete IL-10 in vitro. In contrast, downmodulation of CD5 was accompanied with reduced IL-10 expression and impaired anti-CD3 induced proliferation. Irrespective of the CD3/CD5 phenotype, reduced severity of experimental allergic myelitis occurred in old mice. In MTB TCRβ transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace. These findings suggest that age-associated dysfunctions of the immune system could in part be due to functional erosion of T cells devised to protect the hosts from the prolonged exposure to T cells with high-avidity for self.
    BMC Immunology 02/2012; 13:8. · 2.53 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

[MTBxBXSB]F1 mice
 
[WTxBXSB]F1 controls
 
age-associated reduction
 
autoimmune diseases
 
avidity
 
diverse T cell population
 
diverse T cells
 
effective immunity
 
foreign antigens
 
globally stronger reactivity
 
IL-10 production
 
MTB
 
self-antigens
 
severe autoimmunity
 
T cell receptor
 
T cells
 
therapeutic strategy
 
Tr1 cells
 
Tr1 differentiation
 
transgenic mouse strain
 

M Stojakovic