Delayed activation-induced T lymphocytes death in aplastic anemia: related with abnormal Fas system.
OBJECTIVE
To quantitate apoptosis and Fas antigen expression of T lymphocytes by activation in aplastic anemia (AA) and compare with that of normal controls and completely-recovered AA, and to investigate the apoptotic sensitivity to anti-fas antibody of activated T lymphocytes in AA.


METHODS
We studied the expression of Fas antigen on fresh T lymphocytes of twenty patients with AA [13 newly diagnosed, 7 recorvered AA after immunosuppressive therapy (IST)], and investigated the activation-induced cell death (AICD) and Fas expression by activation [interleukin-2 (200 U/ml) and phytohemagglutinin (50 micrograms/ml)] in 5 newly-diagnosed AA, 5 normal controls and 5 AA in complete response (CR). Apoptotic sensitivity to anti-Fas antibody was assessed by the time-course kinetics of induction of cell death by anti-Fas antibody (500 ng/ml).


RESULTS
There was no significant difference of Fas antigen expression on freshly-isolated T lymphocytes among newly-diagnosed severe AA, normal controls and patients with AA in CR after IST. In normal controls, T lymphocytes death was greatly increased at 3 days of activation, and Fas antigen expression on T lymphocytes was increased above baseline at day 1 of activation. In contrast, in newly-diagnosed AA, T lymphocytes showed delayed cell death, which correlated with a slowed increase of Fas antigen expression by activation. Also, anti-Fas antibody sensitivity of activated T lymphocytes was decreased in newly-diagnosed AA. In completely recovered AA, these abnormal AICD and Fas antigen expressions by activation were recovered to normal range.


CONCLUSIONS
Abnormal AICD plays a role in the immune pathophysiology of AA, and defective Fas system is involved in this process.
Kim
S C
SC
Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Min
Y H
YH
Lee
S
S
Chung
S Y
SY
Yoo
N C
NC
Lee
J W
JW
Hahn
J S
JS
Ko
Y W
YW
D000741:Anemia, Aplastic / Q000276:immunology* / Q000473:pathology; D017209:Apoptosis; D016022:Case-Control Studies; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D013997:Time Factors; D019014:fas Receptor / Q000097:blood
D019014:fas Receptor