A novel mechanism of CD4 lymphocyte depletion involves effects of HIV on resting lymphocytes: Induction of lymph node homing and apoptosis upon secondary signaling through homing receptors

Liqiang Wang, Jenny J Y Chen, Benjamin Gelman, Rolf Konig, Miles W. Cloyd

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Abstract

Recently, we reported that abortive HIV infection of resting human T lymphocytes up-regulated expression of CD62L, the receptor for homing to lymph nodes (LNs), and enhanced homing of these cells from the blood into the LNs (Wang et al., 1997, Virology 228:141). This suggested that HIV-induced homing of resting lymphocytes (which comprise >98% of all lymphocytes) may be a major mechanism for the reduction of CD4+ lymphocytes in the blood of infected individuals. This mechanism also could be partially responsible for the lymphadenopathy that often develops at the same time that CD4+ lymphocytes are disappearing from the blood. In this study, we show that secondary signaling through the homing receptors (CD62L, CD44, CD11a) of abortively infected resting CD4+ T lymphocytes induced apoptosis. These signals would occur as the cells home into the LNs. Apoptosis did not occur after secondary signaling through some other receptors (CD26, CD4, CD45, and HLA class I) or in HIV-exposed resting CD8+ lymphocytes signaled through the homing receptors. These findings indicate that HIV-induced homing of resting CD4+ lymphocytes to LNs results in death of many of these cells. This was confirmed in the LNs of SCID mice that were i.v. injected with HIV-exposed resting human lymphocytes. Thus, these effects of HIV upon binding to resting CD4+ T lymphocytes, which are not permissive for HIV replication, may significantly contribute to their depletion in vivo. These findings also offer an explanation for the bystander effect observed in the LNs of AIDS patients, whereby cells not making virus are dying.

Original languageEnglish (US)
Pages (from-to)268-276
Number of pages9
JournalJournal of Immunology
Volume162
Issue number1
StatePublished - Jan 1 1999

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Lymphocyte Depletion
Lymph Nodes
HIV
Lymphocytes
Apoptosis
T-Lymphocytes
Lymphocyte Homing Receptors
Bystander Effect
CD4 Antigens
Virology
SCID Mice
HIV Infections
Blood Cells
Acquired Immunodeficiency Syndrome
Cell Death
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

A novel mechanism of CD4 lymphocyte depletion involves effects of HIV on resting lymphocytes : Induction of lymph node homing and apoptosis upon secondary signaling through homing receptors. / Wang, Liqiang; Chen, Jenny J Y; Gelman, Benjamin; Konig, Rolf; Cloyd, Miles W.

In: Journal of Immunology, Vol. 162, No. 1, 01.01.1999, p. 268-276.

Research output: Contribution to journalArticle

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