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Suppression of leukemia inhibitor factor in lymphoid tissue in primary HIV infection: absence of HIV replication in gp130-positive cells

Tjernlund, Annelie; Fleener, Zareefaa; Behbahani, Homira; Connick, Elizabethb; Sönnerborg, Andersc; Broström, Christinad; Goh, Li-Eane; Spetz, Anna-Lena; Patterson, Bruce Ka; Andersson, Jan

Basic Science

Background: Leukemia inhibitor factor (LIF), a member of the interleukin-6 cytokine family, has recently been shown to inhibit HIV-1 replication both in vivo and in vitro.

Objective: LIF and its corresponding receptors gp130 and LIF receptor-α (LIFR-α) were studied in lymphoid tissue (LT) to reveal potential systemic immunoregulatory effects during the course of HIV-1 infection.

Methods: LIF, gp130, LIFR-α and HIV-1 replicating cells were identified at the single cell level by immunohistochemistry and quantified by computerized in situ imaging in tonsil and lymph nodes biopsies (LT) from patients with primary HIV-1 infection (PHI), chronic HIV-1 infection (cHI), long-term non-progressors (LTNP) and HIV-1 seronegative controls.

Results: LIF and its receptors, gp130 and LIFR-α were significantly (P < 0.005) upregulated in LT from PHI patients as compared with HIV-1 seronegative controls. Expression of LIF in cHI was comparable to LIF levels in HIV-1 seronegative controls whereas LTNP showed significantly reduced LIF expression (P < 0.05). LIF receptors, gp130 and LIFR-α were significantly upregulated in cHI (P < 0.005) but downregulated in LTNP (P < 0.05 and P < 0.005, respectively). LIF expressing cells could be demonstrated in LT 2 days after onset of acute retroviral syndrome. LIF expression was evident in CD3, CD4 and CD8 cells. Furthermore, high plasma viral load was associated with high expression of LIF in LT. Finally, no HIV-1 replication could be found in CD4 gp130-positive cells in PHI.

Conclusions: LIF, gp130 and LIFR-α showed increased expression in LT from patients with PHI. Furthermore, HIV-1 replication did not occur in cells expressing the LIF signaling receptor, gp130, indicating that LIF may be associated with control of HIV-1 replicating cells in vivo.

From the Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden, the aChildren's Memorial Hospital/North Western University Medical School, Department of Pediatrics, Division of Infectious Diseases, Chicago, Illinois, the bDivision of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA, the cHIV Unit and Center for Infectious Medicine, Department of Medicine, the dDepartment of Medicine and Infectious diseases, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden, and eGlaxo Wellcome R & D, HIV Department, Middlesex, UK.

Correspondence to A. Tjernlund, Center for Infectious Medicine (CIM), Department of Medicine, F59, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, Sweden.

Received: 31 July 2003; revised: 11 February 2003; accepted: 20 February 2003.

© 2003 Lippincott Williams & Wilkins, Inc.