CD2 expression on murine intestinal intraepithelial lymphocytes is bimodal and defines proliferative capacity

The CD2 molecule is normally expressed on nearly all murine lymphocytes, and is co-stimulatory in T cell activation via the antigen receptor (TCR). A naturally occurring T lymphocyte population that is bimodal for CD2 expression was found in the intestinal intraepithelial lymphocytes (IEL). TCR alpha beta + IEL contain CD2- and CD2+ cells of approximately equal proportion, while TCR gamma delta + IEL are predominantly CD2-. The proliferative response of IEL to stimulation with an anti-CD3 mAb or with PMA plus ionomycin co-segregated with CD2 expression; the CD2+ subset proliferated vigorously under these conditions while the CD2- subset was much less responsive. The responding CD2+ IEL contained both TCR alpha beta + and TCR gamma delta + cells. However, activation of the CD2- IEL with anti-CD3 mAb resulted in only the expansion of TCR gamma delta + IEL, while activation with PMA plus ionomycin did not promote expansion of either the TCR alpha beta + or the TCR gamma delta + IEL. These findings parallel observations in the autoimmune lpr mouse, where massive numbers of peripheral TCR alpha beta + CD4-CD8- T cells that lack CD2 expression are also hyporesponsive to mitogenic stimulation. The apparent anergy of CD2- TCR alpha beta + IEL, as well as CD2- T cells from lpr mice, demonstrates that the absence of CD2 on TCR alpha beta + T lymphocytes co-segregates with nonresponsiveness.