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Mechanism(s) promoting HIV‐1 infection of primary unstimulated T lymphocytes in autologous B cell/T cell co‐cultures
Author(s) -
Döpper Susanne,
Wilflingseder Doris,
Prodinger Wolfgang M.,
Stiegler Gabriele,
Speth Cornelia,
Dierich Manfred P.,
Stoiber Heribert
Publication year - 2003
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200323932
Subject(s) - biology , antibody opsonization , opsonin , tropism , t cell , antibody , b cell , complement receptor , flow cytometry , antigen , immunology , virus , virology , complement system , immune system
Abstract Resting CD4 + T cells in the lymphoid tissue (LT) are essential producers of virions at the beginning of HIV infection in vivo . We previously developed a model that allowed in vitro infection of non‐prestimulated T lymphocytes in the presence of autologous B lymphocytes and complement. In this study, we try to clarify the mechanism(s) responsible for virus transmission in unstimulated autologous B cell/T cell co‐cultures. Ex vivo analyses of patient plasma samples revealed that HIV was opsonized. Flow cytometry showed that opsonized virus preferentially bound to complement receptor (CR)‐2 on B lymphocytes in primary B cell/T cell co‐cultures. As indicated by cytokine measurements and transwell experiments, soluble factors seemed to play a minor role in enabling infection. Rather, direct interaction between B and T lymphocytes and direct binding of opsonized virus to CR2 on B cells turned out to be essential for productive infection. Antibodies blocking cell‐cell adhesion inhibited p24 antigen production. An anti‐CR2 antibody blocking C3d‐CR2 binding also significantly reduced viral replication. Since the infection of unstimulated T cells by opsonized primary HIV isolates in the presence of B cells was highly efficient independent of the tropism of the virus, this mechanism may be critical in the pathogenesis of HIV.