Immunologic activation during pregnancy: serial measurement of lymphocyte phenotype and serum activation molecules in HIV-infected and uninfected women

Mikyas, Yeshi; Aziz, Najib; Harawa, Nina T.; Gorre, M.; Neagos, Negoitas; Nogueira, M. C. de L.; Wafer, Deborah; Dillon, Maryann; Boyer, Pamela; Bryson, Yvonne J.; Plaeger, Susan

doi:10.1016/s0165-0378(97)00018-1

Cited by 43 publications

(33 citation statements)

References 23 publications

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“…+ cells are increased compared to CD4 + cells [23,24] a similar situation to that which has been observed in treated Graves' patients [14]. This increase of CD8 cells may counteract the dominance of Th2 in pregnant Graves' disease patients.…”

Section: Effect Of the Presence Or Absence Of Cd8 + Cells On Anti-cd4supporting

confidence: 71%

The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves’ disease: the role of CD8+ cells

Uchimura

Itoh

Yamamoto

et al. 2002

Clinical and Experimental Immunology

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SUMMARY The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell activation in Graves’ disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL-10 in patients with Graves’ disease, Hashimoto's thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8-depleted cells by magnetic separation columns, and cultured for 7 days with or without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL-10 by PBMC from patients with Graves’ disease. The CD40- and IL-4-activated production of IL-10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL-10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell-dependent B-cell activation via a CD40 pathway activates CD23+ cells, leading to over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves’ disease.

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Section: Effect Of the Presence Or Absence Of Cd8 + Cells On Anti-cd4supporting

confidence: 71%

The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves’ disease: the role of CD8+ cells

Uchimura

Itoh

Yamamoto

et al. 2002

Clinical and Experimental Immunology

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“…Cytokine imbalances in the mother due to HIV infection (49,68) may also alter T-cell development in utero and the susceptibility of thymocytes to infection, therefore influencing transmission and disease progression in the children. An inverse relationship between IL-7 levels and CD4…”

Section: Vol 76 2002 Replication In the Thymus Of Hiv Isolates Frommentioning

confidence: 99%

Impact of Cytokines on Replication in the Thymus of Primary Human Immunodeficiency Virus Type 1 Isolates from Infants

Pedroza-Martins

Boscardin

Anisman-Posner

et al. 2002

J Virol

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Early infection of the thymus with the human immunodeficiency virus (HIV) may explain the more rapid disease progression among children infected in utero than in children infected intrapartum. Therefore, we analyzed infection of thymocytes in vitro by HIV type 1 primary isolates, obtained at or near birth, from 10 children with different disease outcomes. HIV isolates able to replicate in the thymus and impact thymopoiesis were present in all infants, regardless of the timing of viral transmission and the rate of disease progression. Isolates from newborns utilized CCR5, CXCR4, or both chemokine receptors to enter thymocytes. Viral expression was observed in discrete thymocyte subsets postinfection with HIV isolates using CXCR4 (X4) and isolates using CCR5 (R5), despite the wider distribution of CXCR4 in the thymus. In contrast to previous findings, the X4 primary isolates were not more cytopathic for thymocytes than were the R5 isolates. The cytokines interleukin-2 (IL-2), IL-4, and IL-7 increased HIV replication in the thymus by inducing differentiation and expansion of mature CD27 ؉ thymocytes expressing CXCR4 or CCR5. IL-2 and IL-4 together increased expression of CXCR4 and CCR5 in this population, whereas IL-4 and IL-7 increased CXCR4 but not CCR5 expression. IL-2 plus IL-4 increased the viral production of all pediatric isolates, but IL-4 and IL-7 had a significantly higher impact on the replication of X4 isolates compared to R5 isolates. Our studies suggest that coreceptor use by HIV primary isolates is important but is not the sole determinant of HIV pathogenesis in the thymus.

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“…[22][23][24][25][26][27] It remains unclear whether or not pregnancy in HIV-infected women represents an extra challenge to the impaired immune system. 28,29 The present prospective study was designed to investigate immunologic changes in HIV-infected and HIV-negative pregnant women, as measured by changes in thymic output, lymphocyte subpopulations including naive cells, immune activation, and Tregs as well as cytokine profiles during and after pregnancy. For personal use only.…”

mentioning

confidence: 99%

Dysregulation of CD4+CD25+CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women

Kolte

Gaardbo

Karlsson

et al. 2011

Blood

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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 HIVnegative 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 fetalmaternal tolerance and in part explain the increased risk of abortion in HIVinfected women. (Blood. 2011;117(6): 1861-1868) IntroductionDuring pregnancy, the maternal immune system is exposed to a major challenge. The fetus expresses paternal alloantigens, yet it is not rejected. 1 The association between HY-restricting human leukocyte antigen (HLA) class II alleles and recurrent miscarriage subsequent to a firstborn boy indicates a CD4 ϩ T cell-mediated mechanism in these cases. 2 How the fetus normally evades a maternal immune response is not fully known, but development of fetal-maternal tolerance possibly relies on alterations of both central (thymic) tolerance 3-6 and peripheral tolerance mediated by regulatory T cells (Tregs). [7][8][9][10][11] The thymus is reduced in size and changed in structure during pregnancy, and in mice a substantial loss of thymocyte proliferation occurs from early pregnancy. 5,6,12 This may promote survival of the fetus by reducing production of new potentially fetus-reactive T cells. Both thymic size and function return to normal postpartum. 6 Likewise, peripheral tolerance is altered during pregnancy; levels of Tregs are expanded during both murine and human pregnancy. [7][8][9][10][11] This expansion is crucial to fetal survival, and lack of mobilization of Tregs may terminate the pregnancy in abortion. 7,9 A delicate balance of Th1-Th2 cytokines directed toward a Th2-dominant pattern is also considered a very important mechanism in favor of pregnancy success. [13][14][15] Knowledge of immunologic changes during pregnancy in HIV-infected women is limited. An increased risk of spontaneous abor...

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Immunologic activation during pregnancy: serial measurement of lymphocyte phenotype and serum activation molecules in HIV-infected and uninfected women

Cited by 43 publications

References 23 publications

The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves’ disease: the role of CD8+ cells

The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves’ disease: the role of CD8+ cells

Impact of Cytokines on Replication in the Thymus of Primary Human Immunodeficiency Virus Type 1 Isolates from Infants

Dysregulation of CD4+CD25+CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women

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