title: Dysregulation of CD4+CD25+CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women.
abstract: Pregnancy represents a major challenge to immunologic tolerance. How the fetal "semiallograft" evades maternal immune attack is unknown. Pregnancy success may involve alteration of both central (thymic) and peripheral tolerance mechanisms. HIV infection is characterized by CD4(+) T-cell depletion, chronic immune activation, and altered lymphocyte subsets. We studied immunologic consequences of pregnancy in 20 HIV-infected women receiving highly active antiretroviral therapy (HAART), and for comparison in 16 HIV-negative women. Lymphocyte subsets, thymic output, and cytokine profiles were measured prospectively during pregnancy and postpartum. A significant expansion of CD4(+)CD25(+)CD127(low)FoxP3(+) regulatory T cells indicating alteration of peripheral tolerance was seen during second trimester, but only in HIV-negative women. HIV-infected women had lower CD4 counts, lower thymic output and Th-2 cytokines, and more immune activation at all time points compared with controls. Immune activation was decreased in HIV-infected patients during pregnancy. In contrast, CD4 counts were increased in both groups. In conclusion, the study does not indicate that pregnancy adversely affects the immunologic course of HIV infection. However, despite HAART during pregnancy, HIV-infected women display different immunologic profiles from HIV-negative women, which may have importance for the induction of fetal-maternal tolerance and in part explain the increased risk of abortion in HIV-infected women.
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark. lilian@kolte.dk
authors.forename: Lilian
authors.initials: L
authors.lastname: Kolte
authors.forename: Julie C
authors.initials: JC
authors.lastname: Gaardbo
authors.forename: Ingrid
authors.initials: I
authors.lastname: Karlsson
authors.forename: Anna Louise
authors.initials: AL
authors.lastname: Sørensen
authors.forename: Lars P
authors.initials: LP
authors.lastname: Ryder
authors.forename: Kristin
authors.initials: K
authors.lastname: Skogstrand
authors.forename: Steen
authors.initials: S
authors.lastname: Ladelund
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation; D049590:Postpartum Period / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000276:immunology*; D011262:Pregnancy Trimester, Second / Q000276:immunology; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit