CD5 B cells are induced by IP injection of basic protein specific CD4 T cells: A possible role of CD5 B cells in EAE

16o CONTROL OF CHRONIC RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (CREAE) REQUIRES THE USE OF N E U R O A C r I V E COMPOUNDS J.K. O'Neill, D. Baker, A.N. Davison and J.L. Turk. Pathology Department, The Royal College of Surg~-.o~sof England, London WC2A 3PN, UK. Following sensitization of Biozzi AB/H mice, autoaggressive cells are generated in the peripheral lymphoid tissue leading to a reproducible and predictable form of CREAE. This provides a means for examining therapeutic agents and strategies for the control of ' immune-mediated CNS disease. Peripheral administration of immanosuppressive agents such as brequinar sodium (DUP 785, repeated doses) or mitoxantrone (MX, single dose) from day 9 post-inoculation (pi.) can successfully prevent acute phase disease. However if treatment is delayed until day 12 pi. (one day before the expected onset of disease) two profiles have been observed: [A] with compounds which fail to cross the blood-brain barrier (BBB), eg. DUF 785, 15-dcoxyspergualin, cycl.osporin A (all given in repeated doses) or MX (single dose), most animals become affected although the severity of the signs may be reduced or [B] the majority of the animals fail to develop clinical disease eg. cyclophosphamide (which enters the CNS, single dose) or MX (repeated doses). Only the compounds in this latter group were highly effective in preventing ongoing relapsing disease. In an attempt to elucidate possible mechanisms of action it has been found that administration of group [A] compounds directly into the CNS on day 12pi. can then prevent disease. Although the efficiency of group [B] compounds could additionally be due to their ability to cause peripheral leucopeania. The data suggests that the general failure of systemically administered compounds to target neuroantigen-specific cells in the CNS, which probably trigger the cascade of events culminating in active disease expression, is in pan due to the impermeability of the BBB preventing otherwise therapeutic doses being achieved.

CD5 B CELLS ARE INDUCED BY IP INJECTION OF BASIC PROTEIN SP~.CIFIC CD4 T CELLS: A POSSIBLE ROLE OF CDS"B CELLS IN EAE Dan Lehmann* and A v r a h a m Ben-Nun, Dept. Cell Biology, Weizmann Institute of Science, Rehovot, Israel. *present adresss Dept. Neurology, Hadassah Hospital, Jerusalem, Israel. Several treatments of EAE were shown to trigger an idiotypic-anti-idintypic interactions in the T cell compartment. In this study we examined the possibility that the inoculation of CD4+ T cells, as done in the process of T cell vaccination, triggers perturbations in i Jiotypic network, not only in the T cell compartment as already shown, but also through the ~timulatio~, of the CD5 B cell population. SJL/J mice were injected ip with irradiated MBP-specific T cell clones. The effect of the injected T cells on lymphocyte subpopulations in the peritoneum was studied. FACS analysis was performed following two consecutively given ip injections of 5x 105 irradiated MBP specific CD4+ T cells. Naive SJL~'Imice have no detectable CD5 B cells, whereas treated mice had profound increase (on 1he evarage 7%) in the proportion of peritoneal cells expressing both CD5 and lgM smface markers. Furthermore, we found that exudate peritoneal cells from treated mice, were able to block in vitro proliferation of T cell lines exposed to either specific antigen or Con A. The proliferation of normal spleen cells in response to the mitogens LPS and Con A was also blocked with a dose of peritoneal exudate cells. Sorting out of CD5+IgM+ cells from the peritoneal exudate indicated that the described inhibitory effect can be atributed to the induced CD5 B ce!is. This indicates that CD5 B cells may have a regulatory role i'n the pathogenesis of EAE.