The function of the CD2 protein is abnormal in multiple sclerosis.
In active multiple sclerosis (MS), T cell adhesion to sheep red blood cells (SRBC) is deficient. The CD2 protein mediates adhesion to SRBC. Since ligands that bind CD2 can activate T cells, we studied adhesion and activation through CD2 in leukocytes from MS patients. Mononuclear cells (MNC) from patients with MS formed markedly fewer avid T cells (TA; T cells binding greater than or equal to 10 SRBC) than MNC from controls. CD2 antigen expression as measured by FACS analysis on T cells and on T cell subsets was equivalent in MS and controls and rose to a comparable extent in both groups after cell activation; yet activated MS MNC continued to form fewer TA than control cells. Avid rosette formation may be reduced by prostaglandins (PG) secreted by monocytes. Exposure to PG in vitro decreased TA% only in controls, suggesting refractoriness to exogenous PG in MS, perhaps because endogenous PG had already acted. The finding that indomethacin increased TA in MS cells favors this formulation. MNC were activated through CD2 using mAb 9-1 paired with mAb 9.6. Proliferation was significantly diminished in MNC from MS patients compared to MNC from normal controls. Thus, even though T cell membrane expression of CD2 appeared normal in MS, adhesion to SRBC and activation through the CD2 protein were defective.
Department of Neurology, University of Chicago Medical Center, IL 60637.
A T
AT
Reder
B G
BG
Arnason
D
D
Maimone
D
D
Rohwer-Nutter
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018801:CD2 Antigens; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009103:Multiple Sclerosis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012397:Rosette Formation; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007375:Interleukin-1; D011971:Receptors, Immunologic; D000527:Alprostadil