title: Suppression of leukemia inhibitor factor in lymphoid tissue in primary HIV infection: absence of HIV replication in gp130-positive cells.
abstract: 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-alpha (LIFR-alpha) were studied in lymphoid tissue (LT) to reveal potential systemic immunoregulatory effects during the course of HIV-1 infection.
  
  
  METHODS
  LIF, gp130, LIFR-alpha 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-alpha 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-alpha 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-alpha 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.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Tjernlund
authors.forename: Zareefa
authors.initials: Z
authors.lastname: Fleener
authors.forename: Homira
authors.initials: H
authors.lastname: Behbahani
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Connick
authors.forename: Anders
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: Christina
authors.initials: C
authors.lastname: Broström
authors.forename: Li-Ean
authors.initials: LE
authors.lastname: Goh
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Spetz
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Patterson
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009025:Morpholines / Q000378:metabolism*; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000032:analysis; D053606:Receptors, OSM-LIF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D016655:HIV Core Protein p24; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D018832:Molecular Chaperones; D009025:Morpholines; D011506:Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; C005759:2-phenyl-5,5-dimethyltetrahydro-1,4-oxazine