Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T-cell responses and expression of immunosuppressive markers.
Adolescent
Adult
CD4-Positive T-Lymphocytes
/ drug effects
CD8-Positive T-Lymphocytes
/ drug effects
CTLA-4 Antigen
/ metabolism
Cells, Cultured
Contraceptive Agents, Female
/ pharmacology
Female
Humans
Immunophenotyping
Lymphocyte Activation
Medroxyprogesterone Acetate
/ pharmacology
Norethindrone
/ analogs & derivatives
Programmed Cell Death 1 Receptor
/ metabolism
Young Adult
depot medroxyprogesterone acetate
norethisterone enanthate cytotoxic T-lymphocyte associated protein-4
programmed cell death-1
Journal
American journal of reproductive immunology (New York, N.Y. : 1989)
ISSN: 1600-0897
Titre abrégé: Am J Reprod Immunol
Pays: Denmark
ID NLM: 8912860
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
26
07
2019
revised:
07
10
2019
accepted:
22
10
2019
pubmed:
16
11
2019
medline:
20
1
2021
entrez:
16
11
2019
Statut:
ppublish
Résumé
Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net-En). Peripheral blood mononuclear cells collected from women aged 18-34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net-En (n = 36) and from women initiating copper intrauterine device (CU-IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T-cells expressing programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4). Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T-cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net-En users, no differences in CD4+CTLA4+ T-cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD-1+ (P < .001) and CD8+PD-1+ (P < .001) T-cells at nadir concentrations. Number of CD4+PD-1+ and CD8+PD-1+ T-cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net-En initiation (P < .001 and P < .001). In CU-IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD-1+ (P = .083) and CD8+PD-1+ (P = .936) compared to baseline. Activation of T-cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.
Identifiants
pubmed: 31729087
doi: 10.1111/aji.13210
pmc: PMC7900783
mid: NIHMS1597141
doi:
Substances chimiques
CTLA-4 Antigen
0
CTLA4 protein, human
0
Contraceptive Agents, Female
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Medroxyprogesterone Acetate
C2QI4IOI2G
norethindrone enanthate
HY3S2K0J0F
Norethindrone
T18F433X4S
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13210Subventions
Organisme : NIAID NIH HHS
ID : R01 AI102835
Pays : United States
Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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