Divergent immunomodulatory effects of recombinant and urinary-derived FSH, LH, and hCG on human CD4+ T cells.
This study investigated the in vitro immune-modulating activities of recombinant versus highly purified urinary follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) at the cellular level. CD4(+) T cells were isolated from peripheral blood mononuclear cells obtained from ten healthy women (aged 19-30 years) with regular menstrual cycles during the follicular phase of their cycle. CD4(+) T cells were stimulated with anti-CD3/CD28 monoclonal antibodies as a T cell-specific mitogen. Proliferative and cytokine responses were analyzed at standard time points (72h). Recombinant FSH (r-FSH) and LH (r-LH) alone showed a modest capacity to influence proliferation and cytokine release by CD4(+) T cells. Conversely, their addition to T cells in combination with recombinant hCG (r-hCG) induced a powerful down-modulation of T cell proliferation, decreased interferon-gamma (IFN-gamma) secretion and increased interleukin-10 (IL-10) production. These immune-modulating activities were not present when CD4(+) T cells were stimulated either in the presence of urinary-purified FSH (u-FSH) or human menopausal gonadotropin (HMG), alone or in combination with recombinant hCG. We are the first to suggest that urinary-purified gonadotropins do not display profound immune-modulating activities as compared with the recombinant preparations, despite their endocrine effects. Therefore, the use of the recombinant preparations in assisted reproductive techniques might be relevant not only for their well-documented endocrine actions but also for their impact on the transient immune tolerance known to favour embryo implantation and progression of pregnancy.
Carbone
Fortunata
F
Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Napoli, Italy.
Procaccini
Claudio
C
De Rosa
Veronica
V
Alviggi
Carlo
C
De Placido
Giuseppe
G
Kramer
Daniel
D
Longobardi
Salvatore
S
Matarese
Giuseppe
G
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007986:Luteinizing Hormone / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014556:Urine / Q000737:chemistry / Q000502:physiology
D006063:Chorionic Gonadotropin; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone