Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis.
SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139-151-specific T cells in the naive repertoire of SJL mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139-151-reactive T cells in both strains by using IAs/PLP 139-151 tetramers. SJL and B10.S mice had similar frequencies of tetramer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the majority of PLP 139-151 tetramer-positive cells were in the CD4+CD25- population, whereas there were more tetramer-positive cells in the CD4+CD25+ population of B10.S mice. Depletion of CD4+CD25+ cells in vivo facilitated the expansion of PLP 139-151-reactive cells with production of T helper 1 cytokines in EAE-resistant B10.S mice. Furthermore, anti-CD25 Ab treatment before immunization resulted in EAE induction in these otherwise resistant mice. These data indicate an important role for autoantigen-specific CD4+CD25+ cells in genetic resistance to autoimmunity.
Reddy
Jayagopala
J
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Illes
Zsolt
Z
Zhang
Xingmin
X
Encinas
Jeffrey
J
Pyrdol
Jason
J
Nicholson
Lindsay
L
Sobel
Raymond A
RA
Wucherpfennig
Kai W
KW
Kuchroo
Vijay K
VK
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D051379:Mice; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D015704:CD4 Antigens; D018991:Myelin Proteolipid Protein; D015375:Receptors, Interleukin-2