CD8(+) T cells in human uterine endometrial lymphoid aggregates: evidence for accumulation of cells by trafficking

Lymphoid aggregates (LA) develop during the proliferative phase of the mens trual cycle in the hyman uterine endometrium (EM). They contain mostly CD8( +) T cells and B cells. As these LA are absent immediately following menses , they may arise by division of cells resident in the EM, or by division of a limited number of precursor cells that traffic into the EM during the ea rly proliferative phase of the menstrual cycle. Alternatively, they may ari se by the continuous trafficking of cells into the EM throughout the prolif erative phase of the menstrual cycle. In this study we investigated the dis tribution and frequency of CD8(+) T cells in the aggregates using expressio n of V beta2 or V beta8 as markers of clonality and Ki-67 as a marker of di viding cells. Confocal microscopic analysis of endometrial tissues showed t he random distribution of CD8(+) T cells within aggregates within the same sample and in aggregates from different samples. Furthermore, comparisons o f the distribution of V beta2 and Vb8 with expected values predicted from P oisson distribution values were not significantly different, suggesting tha t CD8(+) T cells do not arise by division from single precursors. A low lev el of T-cell division within LAs was confirmed by positive staining for Ki- 67. Dividing T cells were randomly dispersed throughout the LA and the freq uency of dividing cells did not vary greatly between aggregates within the same tissue. Nearest-neighbour analysis of dividing cells showed no statist ically significant deviations from a random distribution. Taken together, t hese results suggest that LA develop during the menstrual cycle largely by the trafficking of cells to nucleation sites within the EM, rather than by division of a limited number of precursor cells.