T cells of atomic bomb survivors respond poorly to stimulation by Staphylococcus aureus toxins in vitro: does this stem from their peripheral lymphocyte populations having a diminished naïve CD4 T-cell content?
We found previously that the peripheral CD4 T-cell populations of heavily exposed A-bomb survivors contained fewer naïve T cells than we detected in the corresponding unexposed controls. To determine whether this demonstrable impairment of the CD4 T-cell immunity of A-bomb survivors was likely to affect the responsiveness of their immune systems to infection by common pathogens, we tested the T cells of 723 survivors for their ability to proliferate in vitro after a challenge by each of the Staphylococcus aureus toxins SEB, SEC-2, SEC-3, SEE and TSST-1. The results presented here reveal that the proliferative responses of T cells of A-bomb survivors became progressively weaker as the radiation dose increased and did so in a manner that correlated well with the decreasing CD45RA-positive (naïve) [but not CD45RA-negative (memory)] CD4 T-cell percentages that we found in their peripheral blood lymphocyte (PBL) populations. We also noted that the T cells of survivors with a history of myocardial infarction tended to respond poorly to several (or even all) of the S. aureus toxins, and that these same individuals had proportionally fewer CD45RA-positive (naïve) CD4 T cells in their PBL populations than we detected in survivors with no myocardial infarction in their history. Taken together, these results clearly indicate that A-bomb irradiation led to an impairment of the ability of exposed individuals to maintain their naïve T-cell pools. This may explain why A-bomb survivors tend to respond poorly to toxins encoded by the common pathogenic bacterium S. aureus.
Kusunoki
Yoichiro
Y
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan. ykusunok@rerf.or.jp
Yamaoka
Mika
M
Kasagi
Fumiyoshi
F
Hayashi
Tomonori
T
Koyama
Kazuaki
K
Kodama
Kazunori
K
MacPhee
Donald G
DG
Kyoizumi
Seishi
S
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D002455:Cell Division / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007564:Japan; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D009689:Nuclear Warfare; D011847:Radioactive Fallout; D013211:Staphylococcus aureus / Q000378:metabolism; D017741:Survivors; D013601:T-Lymphocytes / Q000528:radiation effects*
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D011847:Radioactive Fallout; D017493:Leukocyte Common Antigens