Steroid treatments in mice do not alter the number and function of regulatory T cells, but amplify cyclophosphamide-induced autoimmune disease.
Corticosteroids are commonly used in the therapy of autoimmune disease (AID), although they are rarely, if ever, curative. This failure may result from their deleterious effects on regulatory T cells (Treg). In this work, we directly tested the effects of hydrocortisone (HC) administration on Treg number and function in established mouse models of multiple sclerosis and colitis. Treatment with pertussis toxin (Ptx) or Cyclophosphamide (Cyp), two compounds known to affect Treg function served as controls. We first show that contrarily to Ptx, HC administration to mice transgenic for a TCR specific to myelin basic protein induces a mild lymphopenia, without selective depletion of Treg, nor induction of experimental autoimmune encephalomyelitis (EAE). We next report that HC administration to normal mice has no effect on Treg suppressive function tested in vitro. Moreover, we document that Treg isolated from HC-treated animals maintain their capacity to prevent T cell-induced colitis. In contrast, the combined administration of HC and Cyp, as is frequently used in the therapy of severe AID, dramatically enhanced the deleterious effect of Cyp on Treg number and function. Our analysis indicates that while a short course of corticosteroids alone is not deleterious to immune regulation, combined therapies, notably with Cyp, should be avoided.
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, Portugal. mffontes@igc.gulbenkian.pt
Maria Francisca
MF
Moraes-Fontes
Manuel
M
Rebelo
Iris
I
Caramalho
Santiago
S
Zelenay
Marie-Louise
ML
Bergman
António
A
Coutinho
Jocelyne
J
Demengeot
D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D003092:Colitis / Q000276:immunology* / Q000517:prevention & control; D003520:Cyclophosphamide / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008231:Lymphopenia / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D000893:Anti-Inflammatory Agents; D018398:Homeodomain Proteins; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D006854:Hydrocortisone