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T‐cell responses after haematopoietic stem cell transplantation for aggressive relapsing–remitting multiple sclerosis
Author(s) -
Burman Joachim,
Fransson Moa,
Tötterman Thomas H.,
Fagius Jan,
Mangsbo Sara M.,
Loskog Angelica S. I.
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12129
Subject(s) - natalizumab , multiple sclerosis , immunology , t cell , medicine , transplantation , myelin oligodendrocyte glycoprotein , stem cell , biology , experimental autoimmune encephalomyelitis , immune system , microbiology and biotechnology
Summary Autologous haematopoietic stem cell transplantation ( HSCT ) for relapsing–remitting multiple sclerosis is a potentially curative treatment, which can give rise to long‐term disease remission. However, the mode of action is not yet fully understood. The aim of the study was to evaluate similarities and differences of the CD 4 + T ‐cell populations between HSCT ‐treated patients ( n = 12) and healthy controls ( n = 9). Phenotyping of memory T cells, regulatory T ( T reg) cells and T helper type 1 ( T h1) and type 17 ( T h17) cells was performed. Further, T ‐cell reactivity to a tentative antigen, myelin oligodendrocyte glycoprotein, was investigated in these patient populations. Patients treated with natalizumab ( n = 15) were included as a comparative group. White blood cells were analysed with flow cytometry and T ‐cell culture supernatants were analysed with magnetic bead panel immunoassays. HSCT ‐treated patients had similar levels of T reg cells and of T h1 and T h17 cells as healthy subjects, whereas natalizumab‐treated patients had lower frequencies of T reg cells, and higher frequencies of T h1 and T h17 cells. Cells from HSCT ‐treated patients cultured with overlapping peptides from myelin oligodendrocyte glycoprotein produced more transforming growth factor‐β 1 than natalizumab‐treated patients, which suggests a suppressive response. Conversely, T cells from natalizumab‐treated patients cultured with those peptides produced more interleukin‐17 ( IL ‐17), IL ‐1 and IL ‐10, indicating a T h17 response. In conclusion, we demonstrate circumstantial evidence for the removal of autoreactive T ‐cell clones as well as development of tolerance after HSCT . These results parallel the long‐term disease remission seen after HSCT .