Background:  A key question in understanding immune impairment and immune reconstitution in HIV infection is whether functional defects of thymus are involved in alterations of T-cell homeostasis.

Methods:  We evaluated thymic tissue from 4 HIV-infected and from 9 HIV-negative adults who underwent heart surgery. Thymocytes phenotype (CD34, CD1, CD3, CD4, CD8), CD127 and activation/proliferation markers (CD69, CD27, Ki67) were measured, together with the expression of HIV co-receptor (CCR5, CXCR4) and the TCR subsets (TCR ab, TCR gd). T-student test was used for statistical analysis.

Results:  All thymopoietic stages were detected in both HIV⁺ and HIV^– thymic tissues, but these stages were skewed in HIV-infected compared to uninfected thymuses. Thus, whereas the percentage of immature triple negative cells (CD34⁺CD3^–CD4^–CD8^–) was comparable in HIV⁺ and in HIV^– patients, a significant increase of double negative (DN) CD3⁺CD4^–CD8^– cells (14.7% versus 2.3%; p = 0.01) and of CD3⁺CD4^–CD8⁺ single positive (SP) cells (35.5% vs 22.5%) as well as a reduction of double-positive (DP) (CD3⁺CD4⁺CD8⁺:  24.5% vs 31%) and CD3⁺CD4⁺CD8^– SP cells (21.7% vs 37.7%) were observed in HIV⁺ compared to HIV^– subjects. Proliferation and activation status, as evaluated by the expression of Ki67, CD27, and CD69, was significantly augmented in HIV⁺ thymuses both in DN/DP (p <0.05) and in SP thymocytes (p <0.05), with a predominant expression of CD69 in CD4⁺ SP cells. IL-7R expression in HIV⁺ thymuses was significantly reduced in CD34⁺CD3^–CD4^–CD8^– cells (p = 0.01), but was increased in both DP and SP cells. CCR5 and CXCR4 were comparable in HIV-infected and -uninfected thymuses. Nevertheless, whereas CCR5 expression was greater on immature thymocytes in HIV⁺ patients, this HIV coreceptor was mostly expressed by mature thymocytes in HIV- individuals. Finally gdTCR was expressed on a minority of thymocytes subsets in both groups of patients.

Conclusions:  The effect of HIV infection on human thymus seems to act by at least 2 mechanisms:  reduction of intrathymic CD4⁺ precursors and increased activation status of thymocytes at multiple stages of differentiation. Additionally, HIV infection impairs the IL-7/IL-7R circuit in the earlier intrathymic maturation stages (CD34⁺CD3^–CD4^–CD8^–). The higher activation status of immature thymocytes seen in HIV-infected thymuses could explain the increased expression of CCR5 seen in these cells and the augmented susceptibility of thymus to HIV infection.