Decreased number of CD4+ and CD8+ T cells that express the interleukin-7 receptor in blood and tissues of SIV-infected macaques.
Acute HIV/SIV (human/simian immunodeficiency virus) infection results in severe CD4(+) T cell depletion in lymphoid compartments. During the chronic phase of infection, CD4(+) T cell numbers rebound in blood but remain low in the gut-associated lymphoid tissue (GALT), even when viral replication is suppressed by antiretroviral therapy (ART). Thus, strategies to repopulate lymphoid compartments may ameliorate the clinical outcome of HIV/SIV infection. Interleukin (IL)-7 is a key cytokine for the maintenance of homeostatic proliferation of T cells. In HIV/SIV infection, IL-7 expression is increased, likely to compensate for T cell loss, suggesting that supraphysiological administration of IL-7 could provide additional benefit. However, the ability of T cells to respond to IL-7 is dependent on the level of expression of the IL-7 receptor (IL-7R) in T cells in various body compartments. In here, we investigated the proportion of IL-7R(+) T cells in blood, spleen, gut, and genitourinary tract of healthy and SIV-infected macaques with various degrees of CD4(+) T cell depletion. We found that the percentage of T cells expressing IL-7R was significantly lower in both CD4(+) and CD8(+) T cell subsets in SIV-infected macaques than in healthy animals and this decrease directly correlated with the CD4(+) T cell number. Importantly, the proportion of CD4(+) and CD8(+) T cells expressing IL-7R in blood paralleled that found in tissues. IL-7R(+) T cells within the SIV-specific CD8(+) T cells varied and were lowest in most tissues of viremic macaques, likely reflecting continuous antigen stimulation of effector cells.
Moniuszko
Marcin
M
Animal Models and Retroviral Vaccines Section, National Cancer Institute, NCI, 41/D804, Bethesda, MD 20892-5065, USA.
Edghill-Smith
Yvette
Y
Venzon
David
D
Stevceva
Liljana
L
Nacsa
Janos
J
Tryniszewska
Elzbieta
E
Tsai
Wen-Po
WP
Franchini
Genoveffa
G
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008253:Macaca mulatta; D009928:Organ Specificity; D020395:Receptors, Interleukin-7 / Q000097:blood* / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*
D020395:Receptors, Interleukin-7