Defective antigen specific responsiveness in L-selectin deficient mice

L-selectin has been implicated as an important molecule in both lymphocyte homing to peripheral lymph nodes, and neutrophil and monocyte trafficking to inflammatory sites. In order to further elucidate the role of Lselectin in both leukocyte trafficking and the development of the immune system and responses, we have generated germlinebearing L-selectin deficient mice via targeted disruption of this locus. Notably, these animals have very small peripheral lymph nodes, and exhibit the expected inability of leukocytes to show primary adhesion (rolling) on the L-selectin ligand, peripheral node addressin (PNAD). The distribution of subpopulations of T cells and B cells is largely unaltered in L-selectin deficient animals except for apparently compensatory T cell influx into the spleen. Functionally, we have observed a markedly blunted antigenspecific contact hypersensitivity reaction. The respective roles of antigen presenting cells, antigen specific lymphocytes, and effector leukocytes have been characterized. The data suggest a defect more complex than a perhaps expected inability of effector cells to traffic to the inflammatory site. On-going studies using delayed type hypersensitivity models and a broad array of immunolgical parameters to determine the mechanism by which these defective responses arise will be presented.