STIMULATION OF B-CELL LYMPHOPOIESIS BY INTERLEUKIN-7 LEADS TO AGGRAVATION OF MURINE LEISHMANIASIS

The effect of recombinant interleukin-7 (IL-7) on the clinical course of murine leishmaniasis and the development of the accompaning immune response was investigated. Previously, IL-7 has been shown to possess stimulatory capacity for different eel types of the immune and haemato poietic system critically involved in the defence against Leishmania m ajor (L. major), such as macrophages which are activated for the elimi nation of the parasite by IL-7. In contrast to these in vitro data, th e present study indicates that treatment of genetically susceptible BA LB/c mice with IL-7 at the onset of the infection leads to enhanced le sion development and a significantly accelerated death of the animals. This was correlated with a 40-fold increased parasite burden in splee ns and lymph nodes. While the specific antibody response against L. ma jor was not altered and lymphocytes of IL-7-treated mice produced comp arable amounts of the T-helper type-2 (Th2) cytokines IL-4 and IL-10, less interferon-gamma (IFN-gamma) was measurable after antigenic stimu lation of lymph node and spleen cells in vitro. One of the major chang es appearing by the first week after infection in IL-7-treated mice wa s the increase of the total cell number in spleen and lymph nodes drai ning the local infection. Analysis of the cellular composition reveale d that the enhanced cellularity was predominantly due to a rise in the B-cell compartement. Since antigen presentation by B cells has been i mplicated in the development of Th2 cells. the disease-aggravating act ivity of IL-7 is thought to be primarily due to augmentation of B lymp hopoiesis.