Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells
Jinjong Myoung, Don Ganem
Jinjong Myoung, Don Ganem
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Research Article

Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells

Abstract

Kaposi sarcoma–associated herpesvirus (KSHV) is a B-lymphotropic virus whose primary site of replication is the oropharynx. KSHV can infect both T and B cells from primary tonsillar explant cultures. However, T cells do not support lytic replication, while B cells spontaneously produce substantial amounts of infectious virus. Here, we provide evidence for a mechanism by which activated T cells may promote or stabilize latency of KSHV infection in B cells. When mixed cultures of B cells and activated T cells were exposed to KSHV, little spontaneous virus production was observed. Removing T cells from the mix or treating the mixed culture with immune suppressants enhanced virus production. Adding back activated T cells to purified infected B cells efficiently suppressed KSHV production, primarily due to CD4+ T cells. This suppressive activity required T cell activation and direct cell-cell contact, but not prior exposure to KSHV antigen. Suppression was not MHC restricted and did not result in killing of the target cell. We therefore propose that oropharyngeal T cells activated by a variety of stimuli can recognize ligands on infected target B cells, leading to signaling events that prevent spontaneous lytic activation and promote latent infection in this compartment.

Authors

Jinjong Myoung, Don Ganem

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Figure 6

Activated CD4+ T cells are responsible for the inhibition by T cells on viral replication in B cells.

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Activated CD4+ T cells are responsible for the inhibition by T cells on ...
CD3+ T and CD19+ B cells were purified by negative selection as described before. CD4+ T and CD8+ T cells were isolated by positive selection from unfractionated tonsillar cells using beads as in Methods. Purified B cells were infected with rKSHV.219 at MOI 3 for 6 to 12 hours. Excess uninfected viruses were extensively washed. Purified total T, CD4+ or CD8+ T cells, or B cells were activated by PHA or left untreated and added into infected B cells from the same (Autol) or different (Heterol) donors. The determination of IUs was performed as described above. Dots represent data from individual tonsils with background subtracted. The mean of data from 5 different tonsils is indicated by the horizontal bar. ***P < 0.001 by Student’s t test.