Loading...
Please wait, while we are loading the content...
Similar Documents
Effect of CD28/CTLA4 signaling on function of MBP reactive T cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bieganowska, Katarzyna Anderson, David E. Bar-Or, Amit Hafler, David A. |
| Copyright Year | 1998 |
| Abstract | The role of the costimulatory molecule CTLA4 in clonal expansion of MBP reactive T cells was investigated. Direct PCR analysis of T-cell receptor chains expressed by MBP reactive T cells was used to quantify their in vitro response to MBP under different costimulatory conditions. We dissociated costimulatory signals B7.1 and B7.2 by the use of CHO transfectants expressing DR2 and either of the molecules as antigen presenting cells and anti-CTLA4 antibody Fab fragments that block signaling through the CTLA4 molecule. Our results suggest that the proliferation inducing effect of CTLA4 blocking using antibody Fab fragments was dependent on the antigen concentration and on the magnitude of the T-cell response elicited by MBP. B7.1 engagement of CD28 without CTLA4 signal induced clonal expansion of MBP reactive T cells and IFNy secretion while engagement of CD28 with B7.2 induced IL-4 secretion and moderate clonaI expansion. These results are consistent with BT. I expression in MS brain inducing Thl type responses. rhe cfintcal ~l f icaey of ~ i F N l b in reduc ing re lapse r a t a in relapslng-remintng mult ip le sclerosis (MS has been documented and has led to a v~despread prescription of this d r u g Radiological e't idence supports reduction in the nequency of new lesions at MR I. ~IFN ts able t.) induce in v i vo and in v*tro changes in immunological parameters possibly Involved itt b/IS, such as cy tok ines predt lc t lon ( i e , IL-1O and TNF-r 0 and cal l s u r t a d e mok~cl des exwess ion involved in alJtolanligen p¢osf~ntation (such as HI.A-OR). Re~.ent ~h ldi~g~l i n v a l i d a t e d Ih ~ in vitro e l e c t s of ~IFN treatment on adhask~n and transmigration p h e n o m ~ a (Ohib-Jalbut. tf196: Stove. tg98), and in v lvo ogects on so lub le e.dhesion molecule,s concentration n serum (Calabresl. 1997). We evaluated the long term effects of t reatment with ~ IFNlb ( t year) In 10 MS ~0atlents. in rl=~hnct of adk nsion m o l ~ u I n ~ ~nd HI A-OR e x p r n ~ i o n on PBMf~Ca. adhesion phmnomena h ~ t w ~ n PFJM,~KSs a n d endothaSal monolaV¢~r~, and ~VCAM-I ansi gICAM-I ~.onc~antratio,¢l ia sere. At an~ y~ar. a marked dant~sa in the number ot m a n o n t m l ~ r c~lls adher ing to HLJVECs rnonolayers w.ls Observed. sVCAMt levels Incceased dLnill~l JflFN trealment, suggesting that sVCAM-I, rel~ ased upofl endothelial acl ivat ion in in v ivo ~lFN.trealad pallanla, may contr t~0um to b~Jf er the admission phoenorrmna. ThL.~ latter f inding adds intocrnaliort to evaihab[e ev idence of the mechanisms of action c# FIFNIb in ~S~ A signif icant Increa.'¢e in HLA-[SR o n I~lr iphmal blood m o n o c y t ~ wa~ d ~ t a c t e d ; thi= late Incraas~ lrt ~,ct m a l e c l d ~ an P n monocyt~s w ~ ,Jnr~latnd to clinio~t course in our cohort of tient s, since we did observe id aOte~rnent with literature data a sharp reduction In tefepse r~equency dun ~g the year of ~IF N1 b treatment. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/S0165-5728(98)91267-X |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S016557289891267X |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S016557289891267X?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/S0165-5728%2898%2991267-X |
| Volume Number | 90 |
| Journal | Journal of Neuroimmunology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
