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Updated: May 19, 2026
Isolation of Lymphocytes from Mouse Genital Tract Mucosa
Published on: September 3, 2012
Dendritic cell activation and memory cell development are impaired among mice administered medroxyprogesterone
Rodolfo D Vicetti Miguel1, Robert L Hendricks, Alfredo J Aguirre
1Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Abstract:
Epidemiological studies indicate that the exogenous sex steroid medroxyprogesterone acetate (MPA) can impair cell-mediated immunity, but mechanisms responsible for this observation are not well defined. In this study, MPA administered to mice 1 wk prior to HSV type 1 (HSV-1) infection of their corneal mucosa impaired initial expansion of viral-specific effector and memory precursor T cells and reduced the number of viral-specific memory T cells found in latently infected mice. MPA treatment also dampened expression of the costimulatory molecules CD40, CD70, and CD80 by dendritic cells (DC) in lymph nodes draining acute infection, whereas coculture of such DC with T cells from uninfected mice dramatically impaired ex vivo T cell proliferation compared with the use of DC from mice that did not receive MPA prior to HSV-1 infection. In addition, T cell expansion was comparable to that seen in untreated controls if MPA-treated mice were administered recombinant soluble CD154 (CD40L) concomitant with their mucosal infection. In contrast, the immunomodulatory effects of MPA were infection site dependent, because MPA-treated mice exhibited normal expansion of virus-specific T cells when infection was systemic rather than mucosal. Taken together, our results reveal that the administration of MPA prior to viral infection of mucosal tissue impairs DC activation, virus-specific T cell expansion, and development of virus-specific immunological memory.
Insights
Medroxyprogesterone acetate (MPA) impairs immune responses to herpes simplex virus type 1 (HSV-1) mucosal infections by hindering T cell expansion and memory development. This effect is linked to reduced dendritic cell activation and is site-dependent.
Area of Science:
- Immunology
- Virology
- Endocrinology
Background:
- Exogenous sex steroids, like medroxyprogesterone acetate (MPA), are known to affect cell-mediated immunity.
- The precise mechanisms by which MPA influences immune responses, particularly in the context of viral infections, remain incompletely understood.
Purpose of the Study:
- To investigate the impact of MPA administration on T cell responses and immunological memory following herpes simplex virus type 1 (HSV-1) mucosal infection.
- To elucidate the role of dendritic cells (DCs) and costimulatory molecules in MPA-mediated immunomodulation.
Main Methods:
- Mice were treated with MPA prior to HSV-1 corneal infection.
- Analysis of viral-specific T cell expansion, memory T cell populations, and DC costimulatory molecule expression (CD40, CD70, CD80) in draining lymph nodes.
- Ex vivo coculture experiments with DCs and T cells.
- Comparison of mucosal versus systemic infection models.
Main Results:
- MPA treatment prior to HSV-1 mucosal infection impaired the expansion of viral-specific effector and memory precursor T cells.
- Reduced numbers of viral-specific memory T cells were observed in latently infected mice.
- MPA dampened the expression of CD40, CD70, and CD80 on DCs, impairing T cell proliferation.
- Recombinant soluble CD154 (CD40L) administration restored T cell expansion.
- Immunomodulatory effects were dependent on the infection site; systemic infection showed normal T cell expansion.
Conclusions:
- MPA administration before mucosal viral infection impairs DC activation and subsequent virus-specific T cell expansion.
- MPA interferes with the development of robust virus-specific immunological memory following mucosal infection.
- The findings highlight the critical role of DCs and costimulatory pathways in MPA's immunomodulatory effects and emphasize the site-specific nature of these impacts.
