title: IL-7Ralpha expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation.
abstract: Many factors can influence the rate of HIV disease progression, including those that maintain T cell homeostasis. One key homeostatic regulator is the IL-7 receptor (IL-7R). Previous studies have shown IL-7R expression levels decrease in HIV infection, but effects on memory subtypes, CD4(+) T cells, and cell function have not been explored. The present study examined the expression of the IL-7Ralpha chain on naïve and memory T lymphocyte subsets of both HIV-positive and HIV-negative individuals from Nairobi, Kenya to assess the role of IL-7Ralpha in HIV disease. Expression of IL-7Ralpha was significantly reduced in all CD4(+) and CD8(+) T cell subsets in HIV-positive individuals. This reduction was further enhanced in those with advanced HIV progression. Expression of IL-7Ralpha was inversely correlated to immune activation, and apoptosis, and was positively correlated with CD4 count in both bivariate and multivariate analysis. Expression of IL-7Ralpha did not correlate with HIV viral loads, indicating the elevated immune activation seen in HIV-infected individuals may be impacting expression of IL-7Ralpha, independent of viral loads. Signaling via the IL-7R is essential for T cell homeostasis and maintenance of T cell memory. Reduction of this receptor may contribute to the homeostatic disruption seen in HIV.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada, R3E 0 W3.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Koesters
authors.forename: Judie B
authors.initials: JB
authors.lastname: Alimonti
authors.forename: Charles
authors.initials: C
authors.lastname: Wachihi
authors.forename: Lucy
authors.initials: L
authors.lastname: Matu
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Embree
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fowke
mesh_terms: D017209:Apoptosis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D019562:Viral Load
chemical_list: D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain