Impaired function of CD4+/CD25+ T regulatory lymphocytes characterizes the self-limited hepatitis A virus infection.
OBJECTIVE
Hepatitis A virus (HAV) causes a transient illness leaving permanent protection against reinfection. Few data are available on the regulatory mechanisms involved in the CD4+ T helper activation. We aimed to investigate the frequency and function of CD3+/CD4+/CD25+ T cells with regulatory function (Tregs) during acute HAV infection.


METHODS
We enrolled 35 consecutive patients and 15 healthy donors, enumerated Tregs by flow cytometry assay and evaluated, after immunomagnetical sorting with magnetic beads, their ability to inhibit the proliferation of CD4+/CD25- T lymphocytes at different ratios (1:1, 1:10, 1:20).


RESULTS
All patients had the usual course of infection. Our immunological analysis showed Tregs frequency in these patients (6.5% [range, 5-8.8%]; 36 [range, 10-87] cells) did not have any statistical difference compared with healthy donors (6% [range, 5-8%]; 48 (range, 23-71) cells), while their ability to suppress CD4+/CD25- was drastically reduced at different ratios (Mann-Whitney U-test; ratio 1:1, 93% vs 72%, z = -3.34, P < 0.0001; ratio 1:10, 86% vs 51%, z = -4.04, P < 0.001; ratio 1:20, 56% vs 30%, z = -3.43, P < 0.0001). After the seroconversion, CD4+/CD25+ frequency and function in HAV-infected patients did not differ from healthy individuals.


CONCLUSIONS
CD4+/CD25+ T cells seem to be impaired in their function during the HAV acute infection. This evidence might help to determine an optimal T helper cell immune network that is a predisposing factor for a self-limiting disease.
Perrella
Alessandro
A
Department of Hepatogastroenterology and Immunology, VII Division of Infectious Disease and Immunology, Hospital D Cotugno, Naples, Italy. alex.perrel@virgilio.it
Vitiello
Laura
L
Atripaldi
Luigi
L
Sbreglia
Costanza
C
Grattacaso
Stella
S
Bellopede
Pasquale
P
Patarino
Tommaso
T
Morelli
Giuseppe
G
Altamura
Simona
S
Racioppi
Luigi
L
Perrella
Oreste
O
D000328:Adult; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006506:Hepatitis A / Q000276:immunology*; D017957:Hepatitis A Virus, Human / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008213:Lymphocyte Activation; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology
D017252:CD3 Complex; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit