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

AI Article Synopsis

  • HIV-1 infection leads to a reduction in CD4(+) T cells and causes lymphadenopathy, but the mechanisms behind these changes are not fully understood.
  • The study focused on how the HIV-1 envelope glycoprotein, gp120, affects CD4(+) T cell migration markers, revealing that gp120 enhances sensitivity to certain signaling molecules (CCL20 and CCL21) while inhibiting response to another (S1P).
  • Results showed that treatment with gp120 increased the accumulation of CD4(+) T cells in lymph nodes of mice, indicating that gp120 influences T cell movement and may contribute to conditions like lymphopenia and lymphadenopathy without direct HIV infection.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681967PMC
http://dx.doi.org/10.1128/JVI.00130-09DOI Listing

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