Diversity of regulatory CD4 super(+T) cells controlling distinct organ-specific autoimmune diseases

• Published in: Proceedings of the National Academy of Sciences - PNAS 2003-12, Vol.100 (26), p.15806-15811
• Main Authors: Alyanakian, M-A, You, S, Damotte, D, Gouarin, C, Esling, A, Garcia, C, Havouis, S, Chatenoud, L, Bach, J-F
• Format: Article
• Language: English
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2636971100

Depletion of selected regulatory CD4 super(+) T cell subsets induces the spontaneous onset of various immune or autoimmune disorders. It is not clear, however, whether a given subset, notably CD4 super(+)CD25 super(+) regulatory T cells, protects from a wide spectrum of immune disorders, or whether specialized subsets of regulatory T cells control each given disease or group of diseases. We report here, using diabetes prone nonobese diabetic (NOD) mice, that depending on the regulatory T cells that are depleted, i.e., CD25 super(+), CD62L super(+), or CD45RB super(low), distinct immune diseases appear after transfer into NOD severe combined immunodeficiency (SCID) recipients. Thus, reconstitution of NOD SCID mice with CD25 super(-) T cells induces major gastritis and late-onset diabetes, but no or mild colitis. Reconstitution with CD62L super(-) T cells induces fulminant diabetes with no colitis or gastritis. Reconstitution with CD45RB super(high) T cells induces major colitis with wasting disease and no or very moderate gastritis and diabetes. Major differences among the three regulatory T cell subsets are also seen in vitro. The bulk of suppressor cells inhibiting the proliferation of CD4 super(+)CD25 super(-) T cells in coculture is concentrated within the CD25 super(+) but not the CD62L super(+) or CD45RB super(low) T cell subsets. Similarly, cytokine production patterns are significantly different for each regulatory T cell subset. Collectively, these data point to the diversity and organ selectivity of regulatory T cells controlling distinct autoimmune diseases whatever the underlying mechanisms.