Human immunodeficiency virus type 1 gp120 reprogramming of CD4+ T-cell migration provides a mechanism for lymphadenopathy.
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.
Green
Daniel S
DS
Department of Microbiology, The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 01228, USA.
Center
David M
DM
Cruikshank
William W
WW
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D008206:Lymphatic Diseases / Q000276:immunology*; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
D018925:Chemokines; D015699:HIV Envelope Protein gp120; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine