During HIV infection distinct mechanisms drive immune activation of the CD4 and CD8 T cells leading to CD4 T-cell depletion and expansion of the CD8 T-cell pool. This immune activation is polyclonal and extends beyond HIV-specific T cells. One consequence of this immune activation is a profound decrease in IL-7Rα (CD127) expression on memory CD8 T cells. The mechanisms leading to this are unknown and because of the potential impact of reduced IL-7 signaling in memory T cells specific to HIV and other pathogens, in the present study we examined the molecular mechanisms implicated in this downregulation of CD127.
Membrane bound (mIL7RA) and soluble (sIL7RA) mRNA expression was determined by qRT-PCR. CD127, Eomesodermin (Eomes) and T-bet expression in healthy controls and HIV-infected patients were studied by flow cytometry.
CD127 downregulation occurs at the transcriptional level for both mIL7RA and sIL7RA alternative spliced forms in the CD127low memory CD8 T cells. CD127low memory CD8 T cells exhibited increased Eomes expression and an ‘effector-like’ gene profile. These changes were associated with higher HIV-RNA levels. Following combination antiretroviral therapy (cART), there was an increase in CD127 expression over an extended period of time (>5 months) which was associated with decreased Eomes expression.
CD127 is downregulated at a transcriptional level in memory CD8 T cells in association with upregulation of Eomes expression.
aCMRS/Laboratory of Immunoregulation, NIAID
bExperimental Immunology Branch, NCI, NIH, Bethesda
cLaboratory of Molecular Immunoregulation, NCI, NIH, Frederick
dBiostatistics Research Branch, NIAID, NIH, Bethesda
eCollaborative Clinical Research Branch, NIAID, NIH, Frederick, Maryland, USA.
Correspondence to Marta Catalfamo, PhD, Building 10 Room 11B07, CMRS/Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892–1360, USA. Tel: +1 301 496 5309; fax: +1 301 402 4097; e-mail: email@example.com
Received 10 December, 2012
Revised 25 February, 2013
Accepted 21 March, 2013
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