Altered expression of Th1-type chemokine receptor CXCR3 on CD4+ T cells in myasthenia gravis patients

Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte–associated molecule 4–immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.

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TCR Vβ Usage by Acetylcholine Receptor-Specific CD4+T Cells in Myasthenia Gravis

Journal of Autoimmunity ◽

10.1006/jaut.1996.0120 ◽

1997 ◽

Vol 10 (2) ◽

pp. 203-217 ◽

Cited By ~ 10

Author(s):

Raghavanpillai Raju ◽

Duraiswamy Navaneetham ◽

Maria Pia Protti ◽

Robert M. Horton ◽

Bobbi L. Hoppe ◽

...

Keyword(s):

T Cells ◽

Myasthenia Gravis ◽

Acetylcholine Receptor ◽

Cd4 T Cells

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Quantitative features and clinical significance of two subpopulations of AChR-specific CD4+ T cells in patients with myasthenia gravis

Clinical Immunology ◽

10.1016/j.clim.2020.108462 ◽

2020 ◽

Vol 216 ◽

pp. 108462

Author(s):

Xiaoxi Liu ◽

Qian Ma ◽

Li Qiu ◽

Changyi Ou ◽

Zhongqiang Lin ◽

...

Keyword(s):

T Cells ◽

Myasthenia Gravis ◽

Clinical Significance ◽

Cd4 T Cells

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Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4+ T cells in thymomas

Blood ◽

10.1182/blood.v100.1.159 ◽

2002 ◽

Vol 100 (1) ◽

pp. 159-166 ◽

Cited By ~ 76

Author(s):

Philipp Ströbel ◽

Markus Helmreich ◽

Georgios Menioudakis ◽

Sharon R. Lewin ◽

Thomas Rüdiger ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Myasthenia Gravis ◽

Cell Sorting ◽

Cd4 T Cells ◽

Matched Control ◽

Cell Subset ◽

Autoreactive T Cells ◽

T Cell Subset ◽

Age And Sex

Abstract Myasthenia gravis (MG) is the leading paraneoplastic manifestation of thymomas and is probably related to the capacity of thymomas to mature and export potentially autoreactive T cells. Why some thymomas are MG associated (MG+) and others are not (MG−) has been unclear. We addressed this question by comparing the percentages of intratumorous naive mature CD45RA+ thymocytes in 9 MG(+) and in 13 MG(−) thymomas by fluorescence-activated cell sorting analysis. Our results show that intratumorous naive CD4 T cells were present in all MG(+) thymomas and in one MG(−) thymoma with the development of MG only 2 months after surgery. By contrast, the percentage of naive CD4+ T cells was significantly reduced in all 13 MG(−) thymomas (P < .0001). Alterations in intratumorous thymopoiesis were reflected by corresponding alterations of naive T-cell subset composition in the blood, in that only MG(−) patients had significantly decreased levels (P = .02) of naive CD4+ T cells compared with age- and sex-matched control persons. We conclude that paraneoplastic MG is highly associated with the efficiency of thymomas to produce and export naive CD4+T cells. The acquisition of the CD45RA+ phenotype on CD4+ T cells during terminal intratumorous thymopoiesis is associated with the presence of MG in most thymoma patients.

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