Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis.

Olivares-Villagómez D, Wang Y, Lafaille JJ
J Exp Med. 1998 188 (10): 1883-94

PMID: 9815266 · PMCID: PMC2212402 · DOI:10.1084/jem.188.10.1883

The development of T cell-mediated autoimmune diseases hinges on the balance between effector and regulatory mechanisms. Using two transgenic mouse lines expressing identical myelin basic protein (MBP)-specific T cell receptor (TCR) genes, we have previously shown that mice bearing exclusively MBP-specific T cells (designated T/R-) spontaneously develop experimental autoimmune encephalomyelitis (EAE), whereas mice bearing MBP-specific T cells as well as other lymphocytes (designated T/R+) did not. Here we demonstrate that T/R- mice can be protected from EAE by the early transfer of total splenocytes or purified CD4(+) T cells from normal donors. Moreover, whereas T/R+ mice crossed with B cell-deficient, gamma/delta T cell-deficient, or major histocompatibility complex class I-deficient mice did not develop EAE spontaneously, T/R+ mice crossed with TCR-alpha and -beta knockout mice developed EAE with the same incidence and severity as T/R- mice. In addition, MBP-specific transgenic mice that lack only endogenous TCR-alpha chains developed EAE with high incidence but reduced severity. Surprisingly, two-thirds of MBP-specific transgenic mice lacking only endogenous TCR-beta chains also developed EAE, suggesting that in T/R+ mice, cells with high protective activity escape TCR-beta chain allelic exclusion. Our study identifies CD4(+) T cells bearing endogenous alpha and beta TCR chains as the lymphocytes that prevent spontaneous EAE in T/R+ mice.

MeSH Terms (12)

Animals Autoimmune Diseases CD4-Positive T-Lymphocytes Crosses, Genetic Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental Interleukin-4 Mice Mice, Transgenic Myelin Basic Protein Receptors, Antigen, T-Cell Spleen

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