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Terminal Effector CD8 T Cells Defined by an IKZF2+IL-7R- Transcriptional Signature Express FcγRIIIA, Expand in HIV Infection, and Mediate Potent HIV-Specific Antibody-Dependent Cellular Cytotoxicity
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DOI：10.4049/jimmunol.1900422.png)
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Abstract
En 中文
HIV-1 infection expands large populations of late-stage differentiated CD8 T cells that may persist long after viral escape from TCR recognition. In this study, we investigated whether such CD8 T cell populations can perform unconventional innate-like antiviral effector functions. Chronic untreated HIV-1 infection was associated with elevated numbers of CD45RA(+)CD57(+) terminal effector CD8 T cells expressing Fc gamma RIIIA (CD16). The Fc gamma RIIIA(+) CD8 T cells displayed a distinctive transcriptional profile between conventional CD8 T cells and NK cells, characterized by high levels of IKZF2 and low expression of IL7R. This transcriptional profile translated into a distinct NKp80(+) IL-7R alpha- surface phenotype with high expression of the Helios transcription factor. Interestingly, the Fc gamma RIIIA(+) CD8 T cells mediated HIV-specific Ab-dependent cellular cytotoxicity (ADCC) activity at levels comparable with NK cells on a per cell basis. The Fc gamma RIIIA(+) CD8 T cells were highly activated in a manner that correlated positively with expansion of the CD8 T cell compartment and with plasma levels of soluble mediators of antiviral immunity and inflammation such as IP-10, TNF, IL-6, and TNFRII. The frequency of Fc gamma RIIIA(+) CD8 T cells persisted as patients initiated suppressive antiretroviral therapy, although their activation levels declined. These data indicate that terminally differentiated effector CD8 T cells acquire enhanced innate cell-like characteristics during chronic viral infection and suggest that HIV-specific ADCC is a function CD8 T cells use to target HIV-infected cells. Furthermore, as the Fc gamma RIIIA(+) CD8 T cells persist in treatment, they contribute significantly to the ADCC-capable effector cell pool in patients on antiretroviral therapy.
Keywords:
HUMAN-IMMUNODEFICIENCY-VIRUS
NATURAL-KILLER-CELLS
LYMPHOCYTES-T
IMMUNE-RESPONSES
RAKAI DISTRICT
VIREMIA
MEMORY
RECEPTORS
SUBTYPE
BLOOD
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