Quantitation of myelin oligodendrocyte glycoprotein and myelin basic protein in the thymus and central nervous system and its relationship to the clinicopathologic features of autoimmune encephalomyelitis

Abstract

There is controversy whether the amount of autoantigens expressed in the thymus regulates negative selection of autoreactive T cells and determine susceptibility or resistance to experimental autoimmune encephalomyelitis (EAE). In the present study, we have addressed this issue by quantifying neuroantigens in the thymus of two EAE-susceptible (LEW and LEW.1AV1) and one EAE-resistant (BN) rat strains. We further examined whether amounts of neuroantigens in various parts of the central nervous system (CNS) affect the clinical course and lesion distribution of acute and chronic EAE. Real-time PCR and histologic analyses showed that there was no significant difference in the amount and distribution of myelin oligodendrocyte glycoprotein and myelin basic protein in the thymus and CNS among the three strains and that both acute and chronic EAE lesions in the CNS were preferentially distributed in the area where neuroantigens were abundantly present. These findings suggest that susceptibility or resistance to EAE is not regulated by the amount of the neuroantigens expressed in the thymus. Furthermore, the lesion distribution, but not the clinical course, of EAE is related to the neuroantigen expression in the CNS.

Myelin oligodendrocyte glycoprotein induces incomplete tolerance of CD4+ T cells specific for both a myelin and a neuronal self‐antigen in mice

“…In this work, using a previously described semiquantitative approach [7,33], we report thymic expression of MOG in mature mTECs at the mRNA level. Several groups have investigated ectopic expression of self-antigens in the thymus, some succeding in detecting MOG [30,32,33,41], while others reported its absence from the array of thymus-expressed TSA [42]. This lack of consistency in previous findings could be due to the fact that individual TSAs are expressed by only a low proportion of mTECs (1-2%) [3] and with a rapid turnover.…”

“…The 2D2 T cells exhibited increased pathogenic capacity upon recognition of the two self-antigens, demonstrating that both are relevant targets in vivo, a feature we coined cumulative autoimmunity [24]. NF-M [18][19][20][21][22][23][24][25][26][27][28][29][30] shares sequence homology with MOG [38][39][40][41][42][43][44][45][46][47][48][49][50] , including four amino acids that are TCR contact residues for MOG recognition [23,25,26]. These residues are crucial for TCR triggering of NF-M 18-30 -specific clones, proving that bi-specificity arises indeed from molecular mimicry [27].…”