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J Virol. 2009 Jun;83(11):5765-72. doi: 10.1128/JVI.00130-09. Epub 2009 Mar 18.

Human immunodeficiency virus type 1 gp120 reprogramming of CD4+ T-cell migration provides a mechanism for lymphadenopathy.

Author information

1
Department of Microbiology, The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 01228, USA.

Abstract

Infection by human immunodeficiency virus type 1 (HIV-1) is associated with decreases in peripheral CD4(+) T cells and development of lymphadenopathy. The precise mechanisms by which HIV-1 induces these changes have not been elucidated. T-cell trafficking through lymphoid tissues is facilitated by CCL21-mediated entry and sphingosine-1-phosphate (S1P)-mediated egress. Having previously determined that HIV-1 envelop glycoprotein, gp120, directly alters T-cell migration, we investigated whether gp120 without HIV-1 infection could influence the responses of CD4(+) T cells to the signals involved in T-cell trafficking through lymph tissue. Incubation of normal human T cells with gp120 for 1 h resulted in reprogramming of CD4 T-cell migratory responses by increasing sensitivity to CCL20 and CCL21 and complete inhibition of migration to S1P. Incubation of human T cells with gp120 prior to injection into NOD.CB17-Prkdc(scid)/J mice resulted in increases in lymph node accumulation of CD4(+) T cells, with reciprocal decreases in blood and spleen compared to T cells not exposed to gp120. The effects of gp120 required CD4 signaling mediated through p56(lck). These findings suggest that gp120 alone can alter CD4(+) influx and efflux from lymph nodes in a fashion consistent with the development of lymphopenia and lymphadenopathy.

PMID:
19297493
PMCID:
PMC2681967
DOI:
10.1128/JVI.00130-09
[Indexed for MEDLINE]
Free PMC Article

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