Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation

JP Casazza, MR Betts, DA Price, ML Precopio… - The Journal of …, 2006 - rupress.org
JP Casazza, MR Betts, DA Price, ML Precopio, LE Ruff, JM Brenchley, BJ Hill, M Roederer
The Journal of experimental medicine, 2006rupress.org
The role of CD4+ T cells in the control of persistent viral infections beyond the provision of
cognate help remains unclear. We used polychromatic flow cytometry to evaluate the
production of the cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin
(IL)-2, the chemokine macrophage inflammatory protein (MIP)-1β, and surface mobilization
of the degranulation marker CD107a by CD4+ T cells in response to stimulation with
cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes …
The role of CD4+ T cells in the control of persistent viral infections beyond the provision of cognate help remains unclear. We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1β, and surface mobilization of the degranulation marker CD107a by CD4+ T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes. Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4+ T cell maturation. The functional profile of virus-specific CD4+ T cells in chronic CMV infection was unique compared with that observed in other viral infections. Salient features of this profile were: (a) the simultaneous production of MIP-1β, TNF-α, and IFN-γ in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes. This polyfunctional profile was associated with a terminally differentiated phenotype that was not characterized by a distinct clonotypic composition. Thus, mature CMV-specific CD4+ T cells exhibit distinct functional properties reminiscent of antiviral CD8+ T lymphocytes.
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