The effects of lymphotoxin-alpha (LT-alpha) deficiency on mucosal immu
ne status has not been defined. We utilized severe combined immunodefi
ciency (scid) mice as recipients of both mutant and wild-type whole sp
lenocytes to determine whether lymphocytes from mutant mice had impair
ed homing ability. We also utilized irradiated mutant mice as recipien
ts of wildtype whole splenocytes to determine whether lymphoid tissue
anlages had, indeed, failed to develop as a consequence of LT-alpha de
ficiency. Subsequently, all mice were immunized orally with an attenua
ted strain of Salmonella typhimurium and mucosal IgA responses were mo
nitored. The data presented here demonstrate that acid recipients gene
rate mucosal responses equally well when reconstituted with mutant or
wild-type lymphocytes. In contrast, reconstitution of mutant mice with
wild-type cells failed to affect the efficiency of their mucosal immu
nity. The mutant phenotype, therefore, appears to involve neither impa
ired lymphocyte homing nor function in the generation of mucosal immun
ity. However, the mutant phenotype and immune responsiveness cannot be
transformed merely by the provision of LT-alpha-expressing donor cell
populations. The consequence of LT-alpha deficiency on mucosal immune
responsiveness appears to be due to the lack of gut-associated lympho
id tissues, which may include the spleen, in mutant mice, (C) 1998 Aca
demic Press.