T-cell responses to mitogens in atomic-bomb survivors: Radiation effects on mitogen responsiveness are apparent in survivors who had not been diagnosed with cancer prior to testing

Kusunoki Y, Hayashi T, Kyoizumi S
Radiat Res 156(5):564-5, 2001

Summary

In a recent paper in this journal (Kusunoki Y, et al, RERF Report No. 18-99, Radiat Res 155:81-8, 2001) we reported finding significantly fewer T cells that were capable of proliferating in response to concanavalin A (Con A) or of producing interleukin 2 (IL2) in blood samples donated by A-bomb survivors who had been exposed to relatively high (greater than or equal to 1.5 Gy) doses of radiation in Hiroshima than in bloods donated by survivors who had been exposed to much lower doses (<0.005 Gy). We believed that this result could best be explained as an A-bomb radiation effect, but our conclusion to this effect has been challenged by a careful reader who noted that the data from a significant number of test subjects who had previously been diagnosed with cancer had been included in all of the statistical analyses we described. Although we had previously carried out some reasonably extensive statistical analyses to satisfy ourselves that the inclusion of cancer cases in our test populations did not appear to be a confounding variable in reaching our key conclusion, we omitted to include these additional analyses in the published version of our paper. We therefore felt it important to go one step further by testing the possibility that the altered T-cell properties we observed in the more heavily exposed survivors could simply reflect the fact that there were more cancer patients (and hence more patients whose immune status may have been compromised by cancer therapy) in this group than in the less heavily exposed group. This meant recalculating all of our results for those members of both the heavily-exposed and control groups who had not received a diagnosis of cancer at the time of testing, and was accomplished by excluding the data for all 21 low-dose and 26 high-dose individuals with relevant cancer diagnoses from our analyses. The results of these new calculations turned out to differ only marginally from those obtained when none of the cancer cases were excluded (i.e. the new values differ only marginally from those reported in our published paper and upon which our original conclusions were based, and will be made freely available). Our main conclusion is therefore that exposure to A-bomb radiation could well have had a significant and long-lasting negative effect on the capacity of CD4 T-cell populations to produce IL2, and we are now firmly of the belief that this remains true irrespective of any possible effect of cancer therapy (or therapies) on our earlier statistical analyses.