Cell division during thymic selection was studied with a system in which purified populations of T cell antigen receptor (TCR)- CD4+8+ (double-positive [DP]) cells and fetal thymic epithelial cells (TEC) were reaggregated in tissue culture. In this system, immature DP cells differentiate into mature single-positive (SP) CD4+8- and CD4-8+ TCRhi cells within 3-4 d, indicative of positive selection. By adding the DNA precursor, bromodeoxyuridine, to the cultures and staining cells for bromodeoxyuridine incorporation, T cell division in reaggregation cultures was found to be high on day 1, low on day 2, and high on days 4-5. Cell separation studies established that cell division on day 1 was restricted to DP blast cells. In the absence of blast cells, small DP cells failed to proliferate and differentiated into SP cells without cell division, thus indicating that proliferation is not an essential component of positive selection. This applied to SP cells generated within the first 2-3 d. Surprisingly, the SP cells generated later in culture showed a high rate of cell division; the proliferating SP cells were TCRhi and included both CD4+8- and CD4-8+ cells. Turnover of TCRhi SP cells was also prominent in the normal neonatal thymus and in TEC reaggregation cultures prepared with adult lymph node T cells. We speculate that division of mature SP cells in the perinatal thymic microenvironment is driven by stimulatory cytokines released from TEC. Such proliferation could be a device to expand the mature T cell repertoire before export to the periphery.
Article|
October 01 1995
Thymic selection and cell division.
B Ernst
,
B Ernst
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Search for other works by this author on:
C D Surh
,
C D Surh
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Search for other works by this author on:
J Sprent
J Sprent
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Search for other works by this author on:
B Ernst
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
C D Surh
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
J Sprent
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1995) 182 (4): 961–971.
Citation
B Ernst, C D Surh, J Sprent; Thymic selection and cell division.. J Exp Med 1 October 1995; 182 (4): 961–971. doi: https://doi.org/10.1084/jem.182.4.961
Download citation file:
Close