Submitted April 24, 2006
Accepted September 25, 2006
Function of CD4+CD3- cells in relation to B and T zone stroma in spleen
Mi-Yeon Kim, Fiona M McConnell, Fabrina M Gaspal, Andrea White, Stephanie H Glanville, Vasilios Bekiaris, Lucy S Walker, Jorge Caamano, Eric Jenkinson, Graham Anderson, and Peter J Lane*
MRC Centre for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, Birmingham, United Kingdom
* Corresponding author; email: p.j.l.lane{at}bham.ac.uk.
Lymphocytes from lymphotoxin (LT)-alpha deficient mice, which lack segregation of their B and T cell areas, acquire normal organization following adoptive transfer into RAG deficient recipients, identifying a non-B non-T cell in the segregation process. Here we show that a CD4+CD3- accessory cell is tightly associated with discrete vascular cell adhesion molecule-1-expressing stromal cells in B and T cell areas of the mouse spleen. CD4+CD3- cells express high levels of LT
, LT
, and tumor necrosis factor (TNF)-, which are the ligands for the LT receptor and TNFR1 expressed by stromal cells. The expression of these ligands is functional as transferring CD4+CD3- cells derived from either embryonic or adult tissues into LT deficient mice organizes B:T segregation and upregulates CCL21 protein expression in areas where T cells are segregated from B cells. We propose that the function of CD4+CD3- cells is to form a link between primed CD4 T cells and the underlying stromal elements, creating distinct microenvironments in which they enable effector responses.
