Rationale Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. Objective Here we addressed the role of platelets in mediating CNS inflammation in EAE. Results We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control non-diseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression upon platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ib alpha (GPIbα) promotes both platelet adhesion as well as inflammatory actions of platelets, and, targeting of GPIbα attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa) also reduced EAE severity in mice. Conclusions Thus, platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment.

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Measles virus infection causes a profound immunosuppression. The basis for this immunosuppression is not known. This immunosuppression could be due to virus acting directly on lymphoid cells, the production of an immunosuppressive viral product, or a lymphoid product. We have developed an antigen-specific T cell system to study measles virus-T-cell interactions. We demonstrate that as few as five infectious viral particles added to 1000 T cells results in profound inhibition of antigen-specific T cell proliferation. Supernates taken from measles virus-infected T cells suppress the proliferation of uninfected T cells. Measles-virus-infected HeLa or Vero cells do not produce the factor. The antiproliferative effects of the supernates cannot be attributed to infectious virus, IL-10 or TGF-beta. The soluble factor appears to be larger than 100 kDa, yet retains antiproliferative activity following trypsin digestion with a size less than 10 kDa. Loss of activity is seen following heat treatment at 56 degrees C. The factor is lymphoid cell specific and exhibits cytokine-like behavior yet appears not to be a known cytokine. This soluble factor may be responsible for the overt clinical immunosuppression seen in man and a previously undescribed cytokine induced by measles virus infection of human lymphocytes.

Myelin antigen–reactive T cells have been implicated in the pathogenesis of multiple sclerosis (MS). Myelin‐reactive T cells can be isolated from control subjects as well as individuals who have MS. Experimental models of MS indicate that recently stimulated, myelin‐reactive T cells have greater encephalitogenic potential than resting T cells. Activation induces changes in T‐cell surface antigens that may distinguish previously stimulated, memory T cells from naive T cells. Therefore, we examined 108 myelin basic protein (MBP)‐reactive T‐cell lines from 7 MS and 8 control subjects to determine whether MBP‐reactive T cells originated in the memory T‐cell subset or in the naive subset. Isotypes of CD45 were used that designate memory or naive T cells. In subjects having MS, 84% of the MBP‐reactive T cells resided in the memory T‐cell subset. However, in control subjects, only 13% of MBP‐specific T cells originated from the memory T‐cell subset. This result suggests that a substantial proportion of MBP‐reactive T cells from some individuals with MS have been previously activated in vivo. This difference provides additional support for the hypothesis that myelin antigen–specific T cells are involved in the pathogenesis of MS. Ann Neurol 1999;45:33–39