ABNORMAL ORGANIZATION OF THE SPLENIC MARGINAL ZONE AND THE CORRELATEDLEUKOCYTOSIS IN LYMPHOTOXIN-ALPHA AND TUMOR-NECROSIS-FACTOR A DOUBLE DEFICIENT MICE

In this study we further characterized the phenotype at the homeostasi s of mice genetically deficient in Tumor Necrosis Factor-alpha and Lym photoxin-alpha (LT-alpha TNF-alpha(-/-)). As initially observed in LT- alpha(-/-) mice, these mice are devoid of lymph nodes and Peyer's patc hes, while in their spleen the white and red pulp domains are no more detectable, In the blood the leukocytosis dominated by lymphocytosis i s not solely due to the absence of lymph nodes. Indeed, this abnormali ty was shown to be correctable by the transfer of wild type bone marro w in the absence of lymph node, We now report that the metallophilic m acrophages of the marginal zone are no more detectable with an antibod y reactive to sialoadhesin, a macrophage restricted transmembrane mole cule known to bind myeloid and lymphoid cells, The absence of sialoadh esin within the marginal zone, a critical domain for lymphocyte traffi cking towards the white pulp suggests a possible cellular basis for th e observed blood leukocytosis. In addition, in the peritoneal cavity o f LT-alpha TNF-alpha(-/-) mice, the size of the resident leukocyte pop ulation is increased. By their amplitudes these leukocytosis are simil ar within the blood and the peritoneal compartments.