Effect of Thymectomy on Human Peripheral T Cell Pools

G. Sempowski, J. Thomasch, M. Gooding, L. Hale, L. Edwards, E. Ciafaloni, D. Sanders, J. Massey, D. Douek, R. Koup and B. Haynes.

The human thymus is required for establishment of the T cell pool in fetal life, but postnatal thymectomy does not lead to immune deficiency in humans. We have studied the effect of thymectomy on peripheral blood (PB) T cell pool in 10 patients undergoing thymectomy for myasthenia gravis(MG) using surface marker analysis for naive (CD45RA+,CD62L+) and memory (CD45R0+) T cells and signal joint T cell receptor excision circle (sjTREC) analysis. We found thymectomy decreased CD4 and CD8 sjTREC and naive T cell levels in 5/10 patients, all of whom had active thymopoiesis in their thymus at the time of thymectomy. In contrast, of 5 patients in whom sjTREC levels did not fall post-tymectomy, only 1 of 5 had active thymopoiesis present. In 36 thymectomized MG patients studied once at varying times after tymectomy (1 day to 41 years), we found that time after thymectomy was a significant variable in determining PB T cells sjTREC level independent of age. In contrast to the effect on naive T cells, thymectomy induced rises in memory CD4 and/or CD8 T cells in 9 of 10 patients. Total T cell levels rose post-thymectomy in 6/10 patients. Taken together, these data demonstrate selective effects of thymectomy on human naive and memory PB T cell pools. In presence of active thymopoiesis, thymectomy gradually decreased naive T cell levels, whereas thymectomy induced rises in memory PB T cell levels, regardless of the degree of active thymopoieses present at the time of thymectomy. Thus, the human thymus has dual regulatory effects on naive and memory T cell pools. (NIH CA28936, AI44758, AG16826, and CA09058)