Mobilizing monocytes to cross-present circulating viral antigen in chronic infection.

نویسندگان

  • Adam J Gehring
  • Muzlifah Haniffa
  • Patrick T Kennedy
  • Zi Zong Ho
  • Carolina Boni
  • Amanda Shin
  • Nasirah Banu
  • Adeline Chia
  • Seng Gee Lim
  • Carlo Ferrari
  • Florent Ginhoux
  • Antonio Bertoletti
چکیده

Selection of antigens for therapeutic vaccination against chronic viral infections is complicated by pathogen genetic variations. We tested whether antigens present during persistent viral infections could provide a personalized antigenic reservoir for therapeutic T cell expansion in humans. We focused our study on the HBV surface antigen (HBsAg), which is present in microgram quantities in the serum of chronic HBV patients. We demonstrated by quantitative fluorescent microscopy that, out of 6 professional APC populations in the circulation, only CD14 monocytes (MNs) retained an HBsAg depot. Using TCR-redirected CD8+ T cells specific for MHC-I-restricted HBV epitopes, we showed that, despite being constantly exposed to antigen, ex vivo-isolated APCs did not constitutively activate HBV-specific CD8+ T cells. However, differentiation of HBsAg+ CD14 MNs from chronic patients to MN-derived DCs (moDCs) induced cross-presentation of the intracellular reservoir of viral antigen. We exploited this mechanism to cross-present circulating viral antigen and showed that moDCs from chronically infected patients stimulated expansion of autologous HBV-specific T cells. Thus, these data demonstrate that circulating viral antigen produced during chronic infection can serve as a personalized antigenic reservoir to activate virus-specific T cells.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Persistent bovine viral diarrhea virus (BVDV) infection in cattle herds

Bovine viral diarrhea virus (BVDV) is a significant pathogen associated with gastrointestinal, respiratory, and reproductive diseases of cattle worldwide. It causes continuous economic losses to the cattle industry primarily due to decreased reproductive performance. The ability of virus to cross the placenta during early pregnancy can result in the birth of persistently infected (PI) calves. P...

متن کامل

Monocytes from Chronic HBV Patients React In Vitro to HBsAg and TLR by Producing Cytokines Irrespective of Stage of Disease

Individuals who are chronically infected with the hepatitis B virus (HBV) are highly heterogeneous with respect to serum levels of HBV DNA, HBV particles and viral proteins. Since circulating leukocytes, such as monocytes, are constantly exposed to these viral components, it is likely that the functionality of these cells is affected. However, at present, little information is available on the ...

متن کامل

Liver Monocytes and Kupffer Cells Remain Transcriptionally Distinct during Chronic Viral Infection

Due to the scarcity of immunocompetent animal models for chronic viral hepatitis, little is known about the role of the innate intrahepatic immune system during viral replication in the liver. These insights are however fundamental for the understanding of the inappropriate adaptive immune responses during the chronic phase of the infection. We apply the Lymphocytic Choriomenigitis Virus (LCMV)...

متن کامل

Occult Hepatitis B Demonstrated by Anti-HBc and HBV DNA in HIV-Positive Patients

Background: In patients who are hepatitis B virus (HBV) DNA-positive, but HBV surface antigen (HBsAg) -negative, the infection is referred to as occult hepatitis B infection (OBI). Occult HBV infection is harmful when other liver diseases are present, and can aggravate liver damage in in patients with chronic liver diseases. In human immunodeficiency virus (HIV) infection the suppression of vir...

متن کامل

Expanded CD14+ CD16+ monocyte subpopulation in patients with acute and chronic infections undergoing hemodialysis.

Infections are frequent complications in end-stage renal failure patients undergoing hemodialysis (HD), and peripheral blood monocytes are important cells in host defense against infections. The majority of circulating monocytes express high levels of lipopolysaccharide receptor antigen CD14 and are negative for the immunoglobulin Fcgamma receptor type III (CD16). We studied the occurrence of a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of clinical investigation

دوره 123 9  شماره 

صفحات  -

تاریخ انتشار 2013