Increased IL-15 production is associated with higher susceptibility of memory CD4 T cells to simian immunodeficiency virus during acute infection.
Acute SIV infection is characterized by explosive infection of memory CD4 T cells in peripheral and mucosal tissues. Interestingly, relatively few memory CD4 T cells are infected until as late as days 7-8 after challenge. However, by day 10 postinfection, most of the memory CD4 T cells are infected and carry viral DNA. The rapidity with which infection expands within 2-3 days to encompass virtually the entire memory CD4 T cell compartment suggests significant alterations in the susceptibility of memory CD4 T cells to infection during this period. The mechanism(s) underlying this increased permissiveness to infection is not known. In this study, we show that IL-15 secretion significantly correlates with the up-regulated expression of CD4 on memory CD4 T cells that is associated with increased permissiveness to SIV infection. Activation and proliferation of memory CD8, but not memory CD4 T cells, preceded the amplification of viral infection. Although memory CD4 T cells did not express normal activation markers, they displayed a significant up-regulation in the density of CD4 but not CCR5 expression between days 7 and 10 postinfection that correlated with increased plasma IL-15 levels and infection in these cells. Culture of purified CD4 T cells with IL-15 and/or SIV was associated with a significant increase in the expression of CD4 and infection of these sorted cells. Our results demonstrate that IL-15 contributes to the increased susceptibility of memory CD4 T cells to SIV during the early phase of acute SIV infection.
Eberly
Matthew D
MD
Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Kader
Muhamuda
M
Hassan
Wail
W
Rogers
Kenneth A
KA
Zhou
Jianzhong
J
Mueller
Yvonne M
YM
Mattapallil
Mary J
MJ
Piatak
Michael
M
Lifson
Jeffrey D
JD
Katsikis
Peter D
PD
Roederer
Mario
M
Villinger
Francois
F
Mattapallil
Joseph J
JJ
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D053720:Interleukin-15 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit