The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.
We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.
Rohowsky-Kochan
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C
Department of Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, USA.
Molinaro
D
D
Devereux
C
C
Troiano
R
R
Bansil
S
S
Zito
G
G
Wolansky
L
L
Jotkowitz
A
A
Denny
T
T
Oleske
J
J
Dowling
P
P
Cook
S D
SD
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D010919:Placebos; D011241:Prednisone / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D014916:Whole-Body Irradiation
D005938:Glucocorticoids; D010919:Placebos; D011241:Prednisone