Rate of increase in circulating IL-7 and loss of IL-7Ralpha expression differ in HIV-1 and HIV-2 infections: two lymphopenic diseases with similar hyperimmune activation but distinct outcomes.
IL-7 is a nonredundant cytokine for T cell homeostasis. Circulating IL-7 levels increase in lymphopenic clinical settings, including HIV-1 infection. HIV-2 infection is considered a "natural" model of attenuated HIV disease given its much slower rate of CD4 decline than HIV-1 and limited impact on the survival of the majority of infected adults. We compared untreated HIV-1- and HIV-2-infected patients and found that the HIV-2 cohort demonstrated a delayed increase in IL-7 levels during the progressive depletion of circulating CD4 T cells as well as a dissociation between the acquisition of markers of T cell effector differentiation and the loss of IL-7Ralpha expression. This comparison of two persistent infections associated with progressive CD4 depletion and immune activation demonstrates that a better prognosis is not necessarily associated with higher levels of IL-7. Moreover, the delayed increase in IL-7 coupled with sustained expression of IL-7Ralpha suggests a maximization of available resources in HIV-2. The observation that increased IL-7 levels early in HIV-1 infection were unable to reduce the rate of CD4 loss and the impaired expression of the IL-7Ralpha irrespective of the state of cell differentiation raises concerns regarding the use of IL-7 therapy in HIV-1 infection.
Albuquerque
Adriana S
AS
Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Cortesão
Catarina S
CS
Foxall
Russell B
RB
Soares
Rui S
RS
Victorino
Rui M M
RM
Sousa
Ana E
AE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000628:therapy; D015497:HIV-1 / Q000276:immunology; D015498:HIV-2 / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000097:blood* / Q000276:immunology; D008231:Lymphopenia / Q000097:blood* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000276:immunology
D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain