Increased Regulatory T Cell Counts in HIV‐Infected Nonresponders to Hepatitis B Virus Vaccine

Abstract

Hepatitis B virus (HBV) coinfection is a main cause of liver-related mortality in human immunodeficiency virus (HIV)-infected subjects. Unfortunately, HIV-infected subjects show a low rate of response to standard HBV vaccination (23%-56%), in contrast to rates >90% found in the general population, and the underlying causes (particularly cellular and molecular causes) are still unknown. We hypothesized that an increased frequency of regulatory T (T(reg)) cells could be involved in the low rate of seroconversion in HIV-infected subjects. Forty HIV-infected subjects were enrolled in the Assistance Vaccination Program against HBV of the Infectious Diseases Service from the Virgen del Rocío University Hospital, Seville, Spain. Freshly isolated peripheral blood mononuclear cells from baseline were immunophenotyped for T(reg) cells, CD4, and CD8 T cells in both naive and memory subpopulations and activation degree, as well as recent thymic emigrants. Baseline T(reg) cell frequency was found independently associated with the final nonresponse to HBV vaccine in HIV-infected subjects. Furthermore, a negative correlation between baseline frequency of T(reg) cells and antibody titers in the final response was found. These findings suggest an active role played by T(reg) cells on the immunization antigen-specific T and/or B cell responses with the final consequence of a B cell anti-HBs lower production.

Hepatitis B Vaccine Responsiveness and Clinical Outcomes in HIV Controllers

“…A study by Whittall et al [32] demonstrated that the addition of CD40L and IL-4 in vitro were most effective in converting the immunologic signatures of non-controllers to those observed in HIC. Regulatory T-cells (T regs ) also play an important role in modulating immune responses and HBV vaccine response was found to be associated with lower baseline T reg frequency in HIV-infected persons [33]. Individuals with VL suppression, either naturally like HIC or by HAART, have lower levels of T regs compared with untreated persons with HIV [34].…”

Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1

“…61 The number of T regulatory cells is often higher in individuals with HIV than in healthy donors, 62 and is independently associated with non-responsiveness to hepatitis B vaccine in individuals with HIV. 63 T regulatory cells inhibit B cell proliferation by directly inducing apoptosis of proliferating B cells. 64 …”

Hepatitis B vaccination strategy in vaccine low and non-responders: A matter of quantity of quality?

“…Scarce data support this hypothesis, as increased numbers of regulatory T cells (CD4 + CD25 + FoxP3 + ) were demonstrated in the blood of NR after normal hepatitis B vaccination, compared to high-responders, 27 and in hepatitis B vaccine non-responsive HIV-infected subjects. 28 Whether these regulatory T cells are HBsAg specific remains to be investigated.…”