[Proliferation of T lymphocyte subsets in asthma patients in clinical remission and molecular mechanism thereof].
OBJECTIVE
To explore the rule of proliferation of T lymphocyte subsets in patients with clinical asthma remission and the molecular mechanism.


METHODS
Peripheral blood samples were collected from 15 asthmatic patients, 15 asthmatic patients in clinical remission, and 15 healthy control subjects, all sex-, and age-matched. CD(4)(+) T and CD(8)(+) T lymphocytes were isolated. Flow cytometry was used to examine the cell cycles of CD(4)(+) T and CD(8)(+) T lymphocytes. Fluorescence immunohistochemistry was used to detect the expression levels of cell cycle regulatory proteins (CCRPs), including cyclin D, cyclin E, and P27(kip1), PI3K, and STAT6.


RESULTS
(1) The percentage of G(0)/G(1) phase of the CD(4)(+) T lymphocytes of the asthmatic patients was 82.00%, significantly lower than those of the asthmatic patients in clinical remission and healthy controls (92.50% and 99.00%, Z = 12.35, P < 0.01). The percentage of S phase of the CD(4)(+) T lymphocytes of the asthmatic patients was 18.00%, significantly higher than those of the asthmatic patients in clinical remission and healthy controls (6.10% and 0.20% respectively, Z = 8.05, P < 0.05). The percentage of G(2)/M phase of the CD(4)(+) T lymphocytes of the asthmatic patients was 2.80%, significantly higher than those of the asthmatic patients in clinical remission and healthy controls (0.40% and 0 respectively, Z = 9.16, P < 0.05). The S + G(2)/M phase of the CD(4)(+) T lymphocytes of the asthmatic patients was 18.00%, significantly higher than those of the asthmatic patients in clinical remission and healthy controls (7.50% and 0.20% respectively, Z = 12.80, P < 0.05). The distribution of G(0)/G(1) phase of CD(8)(+) T lymphocyte of the asthmatic patients was 44.60%, significantly lower than those of the asthmatic patients in clinical remission and healthy controls (95.90% and 100.00% respectively, Z = 21.60, P < 0.01). The distribution of S phase of CD(8)(+) T lymphocytes of the asthmatic patients was 51.70%, significantly lower than those of the asthmatic patients in clinical remission and healthy controls (0.80% and 0 respectively, Z = 25.22, P < 0.01). The distribution of S + G(2)/M phase of the CD(8)(+) T lymphocytes of the asthmatic patients was 55.40%, significantly higher than those of the asthmatic patients in clinical remission and healthy controls (4.10% and 0 respectively, Z = 21.52, P < 0.01). (2) The expression level of P27(kipl) of the CD(4)(+) T lymphocytes of the asthmatic patients was 13.20%, significant lower than those of the asthmatic patients in clinical remission and healthy controls (38.80% and 47.20% respectively, Z = 10.63, P < 0.01). The expression level of cyclin D of the CD(4)(+) T lymphocyte of the asthmatic patients was 35.00%, significant higher than those of the asthmatic patients in clinical remission and healthy controls (28.20% and 13.10% respectively, Z = 10.66, P < 0.01). The expression level of cyclin E of the CD(4)(+) T lymphocytes of the asthmatic patients was 7.90%, significant higher than those of the asthmatic patients in clinical remission and healthy controls (6.30% and 3.70% respectively, Z = 6.64%, P < 0.05). The expression level of P27(kipl) of the CD(8)(+) T lymphocyte of the asthmatic patients was 4.50%, significant lower than those of the asthmatic patients in clinical remission and healthy controls (33.80% and 46.30% respectively, Z = 9.30, P < 0.05). The expression level of cyclin D of the CD(8)(+) T lymphocyte of the asthmatic patients was 24.20%, not significant different from those of the asthmatic patients in clinical remission and healthy controls (26.10% and 32.20% respectively, Z = 0.09, P > 0.05). The expression level of cyclin E of the CD(8)(+) T lymphocyte of the asthmatic patients was 9.30%, significant higher than those of the asthmatic patients in clinical remission and healthy controls (5.60% and 3.50% respectively, Z = 4.91, P > 0.05). (3) The expression level of PI(3)K-110alpha of the CD(4)(+) T lymphocyte of the asthmatic patients was 7.60%, significant higher than those of the asthmatic patients in clinical remission and healthy controls (6.40% and 3.30% respectively, Z = 9.04, P < 0.05). The expression level of STST()6 of the CD(4)(+) T lymphocyte of the asthmatic patients was 8.20%, significant higher than those of the asthmatic patients in clinical remission and healthy controls (2.70% and 1.90% respectively, Z = 18.08, P > 0.01). The expression levels of PI(3)K-110alpha and STST(6) of the CD(8)(+) T lymphocytes of the asthmatic patients were not significant different from those of the asthmatic patients in clinical remission and healthy controls (Z = 4.91 and 5.70, both P > 0.05).


CONCLUSIONS
There is excessive proliferation of CD(4)(+) T lymphocytes in the patients with clinical asthma remission, which may be related to the abnormal expression of CCRP (cyclin D, cyclin E, and P27(kip1)), PI(3)K, and STAT(6).
Feng
Meng-Jie
MJ
Department of Respiratory, Second College of Clinical Medicine of Jinan University, Shenzhen 518020, China.
Qiu
Chen
C
Chen
Cai-Xia
CX
Li
Fu-Rong
FR
D000328:Adult; D001249:Asthma / Q000097:blood* / Q000473:pathology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012074:Remission Induction