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. 2002 Nov 8;16(16):2119-27.
doi: 10.1097/00002030-200211080-00003.

Entrapment of recent thymic emigrants in lymphoid tissues from HIV-infected patients: association with HIV cellular viral load

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Entrapment of recent thymic emigrants in lymphoid tissues from HIV-infected patients: association with HIV cellular viral load

Mostafa A Nokta et al. AIDS. .

Abstract

Objective(s): Depletion of thymus derived naive T-cells is a feature of HIV infection. Here the impact of HIV infection on the compartmentalization of recent thymic emigrants of (RTE) and naive T-cells was examined.

Methods: Peripheral blood mononuclear cells (PBMC) and lymphoid tissue (LT) from 43 HIV-infected patients and 12 controls were examined for RTE distribution by measuring coding joint T-cell receptor excisional circles (cjTREC) by PCR and naive and memory T-cell subsets and adhesion molecules (L-selection, LFA-1) by flow cytometry.

Results: In HIV-infected patients, the RTE as quantified by cjTRECs in CD4 LT cells were significantly higher than in PBMC. Their values, however, were less than in control subjects, in both the LT and PBMC compartments. This was associated with an increase in L-selectin and LFA-1 expression on LT derived T cells. In PBMC, a significant positive relationship between TREC and naive CD4 cells and an inverse relationship between TREC and cellular viral load (CVL) was observed. Whereas in LT, there was a positive relationship between cjTREC and both naive CD4 cell percentage and CVL.

Conclusions: Collectively, the data suggests that LT is a significant reservoir for RTE. The RTE appeared to be entrapped in LT from HIV-infected subjects. Such entrapment is probably a response to the high viral load in these tissues. These observations may partially explain the decline in RTE observed in the peripheral blood of HIV-infected patients, and the delay in recovery of naive cells in blood after initiation of HAART.

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Figures

Fig. 1
Fig. 1
Relationship of TREC to age (a), absolute CD4 cell counts (b) and circulating HIV plasma RNA (c) of HIV-infected individuals. The trends for these relationships were evaluated statistically using simple linear regression analysis.
Fig. 2
Fig. 2
The relationship of TREC to cellular and plasma viral load in an HIV-infected cohort. The cellular viral load was measured in lymph node (LN) cells and PBMC of HIV-infected subjects. (a) n = 12, (b) n = 13, (c) n = 14.
Fig. 3
Fig. 3
FACS analysis for the expression of LFA-1 on CD4 T cells. The panels showa comparison for the expression of LFA-1 in peripheral blood and lymph nodes obtained from a representative patient infected with HIV.

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