TY - JOUR
T1 - Prior exposure to superantigen can inhibit or exacerbate autoimmune encephalomyelitis
T2 - T-cell repertoire engaged by the autoantigen determines clinical outcome
AU - Prabhu Das, Mercy R.
AU - Cohen, Adam
AU - Zamvil, Scott S.
AU - Offner, Halina
AU - Kuchroo, Vijay K.
N1 - Funding Information:
The authors thank Deepak Kaul for his assistance in generation and maintenance of T-cell hybridomas. We also appreciate Edward Howard and Ritesh Dhar for excellent technical assistance. This work was supported in part by National Institutes of Health Grants R29NS 30843 (VKK), CIDA award NS01771 (SSZ) and NS 23444 (HO) and National Multiple Sclerosis Society Grants RG 2571-A-2 and 2320B3 (VKK). SSZ is a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society.
PY - 1996/12
Y1 - 1996/12
N2 - Experimental allergic encephalomyelitis (EAE) is inducible in experimental animals immunized with myelin basic protein (MBP), proteolipid protein (PLP) or their peptides. We compared T-cell responses to encephalitogenic epitopes of PLP(43-64) and MBP(Ac1-11) in a single mouse strain, (PL/J x SJL)F1. MBP(1-11)-specific T-cell hybridomas expressed predominantly TCR Vβ8 or Vβ4, while PLP(43-64)-specific hybridomas expressed a diverse TCR repertoire. To analyze the biologic significance of the TCR repertoire (limited vs. diverse) to disease susceptibility, we pretreated mice with a superantigen (SEB), and then induced disease with these autoantigens. Mice injected with SEB and immunized with MBP(Ac1-11) showed significant inhibition of EAE, whereas SEB-pretreated mice immunized with PLP(43-64) had an increased severity of EAE and developed a chronic disease. These data demonstrate that prior exposure to microbial superantigens can significantly alter the autoimmune disease course depending upon the TCR repertoire used by the autoantigen.
AB - Experimental allergic encephalomyelitis (EAE) is inducible in experimental animals immunized with myelin basic protein (MBP), proteolipid protein (PLP) or their peptides. We compared T-cell responses to encephalitogenic epitopes of PLP(43-64) and MBP(Ac1-11) in a single mouse strain, (PL/J x SJL)F1. MBP(1-11)-specific T-cell hybridomas expressed predominantly TCR Vβ8 or Vβ4, while PLP(43-64)-specific hybridomas expressed a diverse TCR repertoire. To analyze the biologic significance of the TCR repertoire (limited vs. diverse) to disease susceptibility, we pretreated mice with a superantigen (SEB), and then induced disease with these autoantigens. Mice injected with SEB and immunized with MBP(Ac1-11) showed significant inhibition of EAE, whereas SEB-pretreated mice immunized with PLP(43-64) had an increased severity of EAE and developed a chronic disease. These data demonstrate that prior exposure to microbial superantigens can significantly alter the autoimmune disease course depending upon the TCR repertoire used by the autoantigen.
KW - T-cell receptor usage
KW - experimental autoimmune encephalomyelitis
KW - staphylococcal enterotoxins
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U2 - 10.1016/S0165-5728(96)00107-5
DO - 10.1016/S0165-5728(96)00107-5
M3 - Article
C2 - 8982096
AN - SCOPUS:0030561053
SN - 0165-5728
VL - 71
SP - 3
EP - 10
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -