T lymphocyte subset abnormalities in the blood and lung in pulmonary arterial hypertension.
BACKGROUND
Mounting data suggest that immune cell abnormalities participate in the pathogenesis of pulmonary arterial hypertension (PAH).


OBJECTIVE
To determine whether the T lymphocyte subset composition in the systemic circulation and peripheral lung is altered in PAH.


METHODS
Flow cytometric analyses were performed to determine the phenotypic profile of peripheral blood lymphocytes in idiopathic PAH (IPAH) patients (n=18) and healthy controls (n=17). Immunocytochemical analyses of lymphocytes and T cell subsets were used to examine lung tissue from PAH patients (n=11) and controls (n=11).


RESULTS
IPAH patients have abnormal CD8+ T lymphocyte subsets, with a significant increase in CD45RA+ CCR7- peripheral cytotoxic effector-memory cells (p=0.02) and reduction of CD45RA+ CCR7+ naive CD8+ cells versus controls (p=0.001). Further, IPAH patients have a higher proportion of circulating regulatory T cells (T(reg)) and 4-fold increases in the number of CD3+ and CD8+ cells in the peripheral lung compared with controls (p<0.01).


CONCLUSIONS
Alterations in circulating T cell subsets, particularly CD8+ T lymphocytes and CD4+ T(reg), in patients with PAH suggest that a dysfunctional immune system contributes to disease pathogenesis. A preponderance of CD3+ and CD8+ T lymphocytes in the peripheral lung of PAH patients supports this concept.
Austin
E D
ED
Department of Pediatrics, Division of Pulmonary, Allergy, and Immunology Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. eric.austin@vanderbilt.edu
Rock
M T
MT
Mosse
C A
CA
Vnencak-Jones
C L
CL
Yoder
S M
SM
Robbins
I M
IM
Loyd
J E
JE
Meyrick
B O
BO
D000328:Adult; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006976:Hypertension, Pulmonary / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*