EVER2 deficiency is associated with mild T-cell abnormalities.
Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent flat warts or pityriasis versicolor-like lesions caused by betapapillomaviruses (EV-HPVs). Autosomal recessive EVER1 and EVER2 deficiencies account for EV in most patients. The mechanisms by which mutations in these partners of the Zinc transporter ZnT1 impair host defense against EV-HPVs are still poorly understood. Keratinocytes of EVER-deficient patients display an alteration of zinc homeostasis and an enhanced proliferative activity. Since EVER proteins are highly expressed in T lymphocytes, we aimed to assess the impact of EVER2 deficiency on T-cell development and function. We studied circulating lymphocyte populations in three adult EV patients sharing the same EVER2 mutation (T150fsX3). We found a normal count of CD4(+) and CD8(+) T cells and a normal proliferative capacity in response to anti-CD3 stimulation. However, we observed a significant increase of memory CD4(+) and effector memory CD8(+) T cells, a bias of the TCR Vαβ and Vγδ repertoires and an increase of skin-homing CD4(+) T-cell subsets. Our findings suggest that EVER2-deficient patients display mild T-cell abnormalities. It remains unclear whether these abnormalities result from EVER deficiency, chronic EV-HPV infection, or both.
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Amandine
A
Crequer
Capucine
C
Picard
Vincent
V
Pedergnana
Annick
A
Lim
Shen-Ying
SY
Zhang
Laurent
L
Abel
Slawomir
S
Majewski
Jean-Laurent
JL
Casanova
Stefania
S
Jablonska
Gerard
G
Orth
Emmanuelle
E
Jouanguy
D052686:Betapapillomavirus / Q000472:pathogenicity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002908:Chronic Disease; D004819:Epidermodysplasia Verruciformis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000276:immunology
D008565:Membrane Proteins; C470315:TMC8 protein, human