Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be associated with emergence of syncytium-inducing variants in human immunodeficiency virus type 1-positive individuals

Human immunodeficiency virus type 1 (HIV-1) primary infection is characteri zed by the use of CCR5 as a coreceptor for viral entry, which is associated with the non-syncytium-inducing (NSI) phenotype in lymphoid cells. Syncyti um-inducing (SI) variants of HIV-1 appear in advanced stages of HIV-1 infec tion and are characterized by the use of CXCR4 as a coreceptor. The emergen ce of SI variants is accompanied by a rapid decrease in the number of T cel ls. However, it is unclear why SI variants emerge and what factors trigger the evolution of HIV from R5 to X4 variants. Interleukin-7 (IL-7), a cytoki ne produced by stromal cells of the thymus and bone marrow and by keratin, is known to play a key role in T-cell development. We evaluated IL-7 levels in plasma of healthy donors and HIV-positive patients and found significan tly higher levels in HIV-positive patients. There was a negative correlatio n between circulating IL-7 levels and CD4(+) T-cell count in HIV-positive p atients (r = -0.621; P < 0.001), suggesting that IL-7 may be involved in HI V-induced T-cell depletion and disease progression. IL-7 levels were higher in individuals who harbored SI variants and who had progressed to having C D4 cell counts of lower than 200 cells/<mu>l than in individuals with NSI v ariants at a similar stage of disease. IL-7 induced T-cell proliferation an d up-regulated CXCR4 expression in peripheral blood mononuclear cells in vi tro. Taken together, our results suggest a role for IL-7 in the maintenance of T-cell regeneration and depletion by HIV in infected individuals and a possible relationship between IL-7 levels and the emergence of SI variants.