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Case Reports
. 2019 Jul;144(1):306-309.e2.
doi: 10.1016/j.jaci.2019.02.020. Epub 2019 Mar 1.

T-cell mitochondrial dysfunction and lymphopenia in DOCK2-deficient patients

Mohammed F Alosaimi  1 , Hiba Shendi  2 , Abdallah Beano  3 , Kelsey Stafstrom  3 , Rabab El Hawary  4 , Safa Meshaal  4 , Nermeen Galal  5 , Sung-Yun Pai  6 , Aisha El-Marsafy  5 , Raif S Geha  3 , Janet Chou  7
Affiliations
Case Reports

T-cell mitochondrial dysfunction and lymphopenia in DOCK2-deficient patients

Mohammed F Alosaimi et al. J Allergy Clin Immunol. 2019 Jul.

Abstract

This study delineates the mitochondrial defects in DOCK2-deficient T cells contributing to the T cell lymphopenia characteristic of this primary immunodeficiency.

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Conflict of interest statement

Conflict of interest: The authors declare no conflicts of interest.

Figures

Figure 1. A.
Figure 1. A.
DOCK2 schematic. B. PCR products from a control (C) and P1. C. Sanger sequencing around the mutation in P2 and a control. D. Immunoblot of DOCK2 in PBMCs from a control and patients. E. Mean fluorescence intensity (MFI) of dihydroethidium (DHE) in CD4+ and CD8+ T cells from four controls and patients. F. Extracellular flux analysis of the oxygen consumption rate (OCR) in resting T cells from two controls and patients. G. Numbers of live CD3+ T cells from four controls and patients after 24 hours of anti-CD3+anti-CD28 stimulation. H. MFI of DIOC6, which reflects mitochondrial membrane potential, in CD4+ T cells from four controls and P1 before and after activation. I. MFI of Mitotracker Green (MTG), which reflects mitochondrial mass, in CD4+ T cells from four controls and P1 before and after activation. J, K. MFI of DIOC6 (J) and MTG (K) in CD8+ T cells from four controls and P1 before and after activation. L. Proposed mechanism of mitochondrial dysfunction in DOCK2-deficient T cells. Data for panels E, G – K were pooled from four independent experiments. ns, not significant; *p<0.05; **p<0.01, ***p<0.001; ****p<0.0001 using one-way ANOVA for multiple comparisons or Student’s t test for two groups.
Figure E1.
Figure E1.
MFI of dihydroethidium (DHE) (A), Mitotracker Green (B), and DIOC6 (C) in CD4+ T cells from controls and the chronically infected patient with and without anti-CD3+anti-CD28 stimulation. MFI of dihydroethidium (DHE) (D), Mitotracker Green (E), and DIOC6 (F) in CD8+ T cells from controls and the chronically infected patient with and without anti-CD3+anti-CD28 stimulation.
Figure E2.
Figure E2.
MFI of dihydroethidium (DHE) (A), DIOC6 (B), and Mitotracker Green (C) in EBV-transformed lymphoblastoid B cell line (BLCL) from controls and P1.
See this image and copyright information in PMC

References

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