Interferon-gamma-producing T cells, pregnancy, and postpartum relapses of multiple sclerosis.
OBJECTIVE
To determine whether fluctuations in functional T-cell subsets can explain why multiple sclerosis (MS) relapses decline during pregnancy and increase in the postpartum period.


METHODS
Case-control study.


METHODS
Kaiser Permanente Northern California and Stanford University.


METHODS
Twenty-six pregnant women with MS and 24 age-matched, pregnant controls. Intervention We prospectively followed up the pregnant women with MS and the age-matched, pregnant controls; conducted structured interviews; and collected peripheral blood mononuclear cells during each trimester and 2, 4, 6, 9, and 12 months post partum.


METHODS
Sixteen functional cell types, including interferon-gamma (IFN-gamma)- and tumor necrosis factor-producing T-cell subsets, were measured using multicolor flow cytometry. Since these cell types may also fluctuate with pregnancy, lactational amenorrhea, or MS treatment, the data were analyzed taking into account these factors.


RESULTS
Fifteen women with MS (58%) had relapses during the postpartum year. CD4(+)IFN-gamma-producing cells fluctuated with MS relapses, declining during pregnancy in women with MS (P < .001) and continuing to decline after parturition in women with relapses (P = .001), yet rising or remaining stable in women with nonrelapsing MS or healthy pregnant women. Lactational amenorrhea was associated with a rise in CD4(+)IFN-gamma-producing cells in women with MS (P = .009). In contrast, CD4(+) tumor necrosis factor-producing cells decreased during lactational amenorrhea in all groups of women and, once this was taken into account, obscured any relationship to MS relapses. CD8(+)IFN-gamma-producing cells were elevated in women with MS throughout the study (P < .001) but did not fluctuate with relapses.


CONCLUSIONS
Our findings suggest that a decline in circulating CD4(+)IFN-gamma-producing cells leads to postpartum MS relapses. Our findings also suggest that the decline in these cells may begin during late pregnancy and that lactational amenorrhea induced by exclusive breastfeeding may be able to interrupt this process.
Langer-Gould
Annette
A
Department of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA 94305, USA. annette1@stanford.edu
Gupta
Rohit
R
Huang
Stella
S
Hagan
Adam
A
Atkuri
Kondala
K
Leimpeter
Amethyst D
AD
Albers
Kathleen B
KB
Greenwood
Eleni
E
Van Den Eeden
Stephen K
SK
Steinman
Lawrence
L
Nelson
Lorene M
LM
D000328:Adult; D000568:Amenorrhea / Q000276:immunology; D001942:Breast Feeding; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D007774:Lactation / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000503:physiopathology; D049590:Postpartum Period / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D011264:Pregnancy Trimesters / Q000276:immunology*; D011446:Prospective Studies; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma