Blood. 2004 Feb 19
Crawford MP, Yan SX, Ortega S, Mehta RS, Hewitt RE, Price DA, Stastny P, Douek DC, Koup RA, Racke MK, Karandikar NJ.
Pathology, UT Southwestern Medical Center, Dallas, TX, USA.
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) with features suggestive of T cell-mediated pathology.
The majority of prior reports have focused on CD4+ T cells with the underlying assumption that MS is predominantly a CD4+ Th1-mediated disease.
In this report, we utilized a novel flow cytometric approach to evaluate autoreactive T cell responses against a large variety of neuroantigenic targets.
We found that both CD4+ and CD8+ T cells targeted against several CNS autoantigens were widely prevalent in MS patients and healthy individuals.
Whereas the distribution of CD4+ responses was similar in different groups, patients with relapsing-remitting MS showed a higher proportion of CNS-specific CD8+ responses.
Autoreactive CD4+ T cells from MS patients exhibited a more differentiated Th1 phenotype compared to healthy subjects.
Similarly, CNS-specific CD8+ T cell responses from MS patients were functionally distinct from those in healthy individuals.
Collectively, these studies reveal the high prevalence of Class I-restricted autoreactive CD8+ T cell responses in MS patients that has been underappreciated thus far.
The results emphasize the need to evaluate both CD4+ and CD8+ T cell responses in MS and making both subsets a consideration in the development of novel therapeutic strategies.