Transgenic Expression of Lymphotoxin Restores Lymph Nodes to Lymphotoxin-α-Deficient Mice

Lymphotoxin-α (LTα) has recently been demonstrated to be important in the development of lymph nodes (LN), Peyer's patches, and splenic organization, including the development of germinal centers. To elucidate the role of LTα in lymphoid organogenesis and the plasticity of the process, we examined LTα^-/- mice in which an LTα transgene under the control of the rat insulin promoter (RIPLT) is expressed in the pancreas, kidney, and skin. The LTα transgene restored LN in LTα^-/- mice. The reconstituted LN of RIPLT.LTα^-/- mice had germinal center-like peanut agglutinin-positive regions, but lacked follicular dendritic cells. Although the LTα transgene did not restore Peyer's patches or splenic architecture, it restored the ability of the spleen to form germinal centers and follicular dendritic cell networks. Lymphocytes isolated from the reconstituted LN showed normal proliferative responses to T and B cell mitogens and were defective in their proliferative response to T-dependent Ag, and a decreased number of interdigitating dendritic cells was apparent in the RIPLT.LTα^-/- mice LN. Expression of the RIPLT transgene in mice deficient in LTβ did not reconstitute LN, suggesting an important role for LTβ in the mechanisms that reconstitute LN in RIPLT.LTα^-/- mice. These data are the first to demonstrate reconstitution of LN in LTα^-/- mice and show that the process of LN restoration is amenable to manipulation with ectopic lymphotoxin.