In vitro transendothelial migration of blood T lymphocytes from HIV-infected individuals.
OBJECTIVE
We hypothesized that differential extravasation of circulating CD4+ or CD8+ T lymphocytes contributes to HIV-associated CD8+ lymphocytic alveolitis. Differences in T-cell transendothelial migration may be intrinsic or emerge at sites where vascular endothelium is activated by overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma.


METHODS
We used an in vitro model of lymphocyte extravasation to assess transendothelial migration of peripheral blood mononuclear cells (PBMC) from HIV-positive individuals. We assayed bronchoalveolar lavage (BAL) fluid from HIV-positive and normal individuals to determine if increased levels of TNF-alpha and IFN-gamma were present in the lungs of HIV-infected individuals.


METHODS
Transendothelial migration was assessed by determining the number and flow cytometric phenotype of PBMC adherent to or migrating across unstimulated or TNF-alpha and IFN-gamma-activated endothelial cell monolayers. We measured BAL fluid cytokine concentrations using standard antigen-capture enzyme-linked immunosorbent assays for TNF-alpha and IFN-gamma.


RESULTS
T cells migrating across unactivated endothelial cells were significantly enriched for CD4+ T cells. Cytokine activation of endothelial cells allowed significantly greater transendothelial migration of CD8+ T cells compared to unactivated endothelial cells. TNF-alpha was increased in BAL fluid from HIV-positive individuals relative to controls.


CONCLUSIONS
These data suggest that, in HIV-positive individuals, CD4+ T cells are migration competent and blood CD8+ T cells do not have enhanced migration competence relative to CD4+ T cells. CD8+ T cell extravasation is aided by TNF-alpha and IFN-gamma-induced endothelial cells activation.
Saukkonen
J J
JJ
Pulmonary Center, Boston University School of Medicine, Massachusetts, USA.
Furfaro
S
S
Mahoney
K M
KM
Strieter
R M
RM
Burdick
M
M
Wright
E A
EA
Kornfeld
H
H
Berman
J S
JS
D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma