Suppression of leukemia inhibitor factor in lymphoid tissue in primary HIV infection: absence of HIV replication in gp130-positive cells.
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.
Tjernlund
Annelie
A
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Fleener
Zareefa
Z
Behbahani
Homira
H
Connick
Elizabeth
E
Sönnerborg
Anders
A
Broström
Christina
C
Goh
Li-Ean
LE
Spetz
Anna-Lena
AL
Patterson
Bruce K
BK
Andersson
Jan
J
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
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