The distribution of immunocompetent cells in the genital tract of HIV-positive women

Olaitan, Adeola; Johnson, Margaret; MacLean, Allan; Poulter, L. W.

doi:10.1097/00002030-199606001-00010

Cited by 54 publications

(45 citation statements)

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“…The expected reversal of the CD4 : CD8 ratio is observed in the female LGT [21] as at other mucosal sites [37,38]. T-cell numbers are well maintained, as despite a fall in CD4 1 cell numbers, there is a concomitant rise in CD8…”

Section: Discussionmentioning

confidence: 82%

“…In contrast, the female LGT has not been as extensively studied. Pilot studies in this laboratory have reported distinct changes to several components of the immune repertoire at this site in association with HIV infection [21,22]. However, to this date no comprehensive study has been undertaken which relates the cellular and humoral components of the immune defence system in areas of the LGT of HIV1 women.…”

Section: Introductionmentioning

confidence: 99%

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Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Ahmed¹,

Al-Doujaily²,

Johnson

et al. 2001

Scand J Immunol

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This study investigates the distribution of immunocompetent cells in the ectocervix, and cytokine and immunoglobulin (Ig) levels in cervicovaginal secretions to determine whether they are altered in asymptomatic human immunodeficiency virus (HIV) infection. Ectocervical biopsies from 10 HIV1 and 10 presumed HIV-ve women were studied by immunocytochemistry. Levels of Igs in cervicovaginal secretions were quantified by radial immunodiffusion (RID) and cytokine levels by ELISA. HIV1 women had significantly increased numbers of CD8 1 lymphocytes resulting in reversal of the CD4:CD8 ratio. There was a significant increase in the proportion of activated CD81 HLA-DR1 and CD4 1 HLA-DR 1 lymphocytes, but not in CD81 TIA-11 cells. The epithelium of the cervix from HIV1 subjects showed a significant increase in both numbers of macrophages (CD681) and proportions of activated macrophages (CD681 HLA-DR1) compared to normal. The stroma contained increased proportions of inductive (D11) and suppressive (D11 D71) macrophages but a decrease in effector phagocyte (D71) proportions and Langerhans' cells. Significantly lower tumour necrosis factor (TNF)-a levels were observed in cervicovaginal secretions from HIV1 subjects. IgG levels were 4 times higher and IgM levels twice higher in cervicovaginal secretions from HIV1 women, compared to results from normal subjects. These results suggest a response within the CD8 1 cells in HIV1 women, yet these cells may have a low cytolytic capacity. The raised proportions of HLA-DR1 and D11 CD4 1 macrophages could act as antigen-presenting cells (APC) for CD4 1 CD45RO1 lymphocytes, and represent a local acquired response. However, the close juxtaposition of these cells offers the potential for them to act as a local reservoir of virus and promote its proliferation. The increase of IgG over sIgA in secretions of HIV1 subjects provides evidence suggesting a dysregulation of local humoral immunity.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Ahmed¹,

Al-Doujaily²,

Johnson

et al. 2001

Scand J Immunol

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“…Furthermore, CD4 ϩ and CCR5 ϩ cell populations, which are susceptible to productive HIV-1 infection, are present in this region (31,32). The cervical submucosa is well-supplied with CD8 ϩ T lymphocytes, both of a memory (CD45RO ϩ ) and effector (perforin ϩ ) phenotype (33), and CD3 ϩ cytolytic activity is present in the genital tract throughout the menstrual cycle (31)(32)(33). Therefore, we hypothesize that HIV-1-specific cervical CTL in the submucosa may target susceptible host cells, which have undergone productive infection by HIV-1 after viral transcytosis across the epithelial tight membrane.…”

Section: Discussionmentioning

confidence: 99%

HIV-1-Specific Mucosal CD8+ Lymphocyte Responses in the Cervix of HIV-1-Resistant Prostitutes in Nairobi

Kaul

Plummer

Kimani

et al. 2000

The Journal of Immunology

345

228

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Understanding how individuals with a high degree of HIV exposure avoid persistent infection is paramount to HIV vaccine design. Evidence suggests that mucosal immunity, particularly virus-specific CTL, could be critically important in protection against sexually acquired HIV infection. Therefore, we have looked for the presence of HIV-specific CD8+ T cells in cervical mononuclear cells from a subgroup of highly HIV-exposed but persistently seronegative female sex workers in Nairobi. An enzyme-linked immunospot assay was used to measure IFN-γ release in response to known class I HLA-restricted CTL epitope peptides using effector cells from the blood and cervix of HIV-1-resistant and -infected sex workers and from lower-risk uninfected controls. Eleven of 16 resistant sex workers had HIV-specific CD8+ T cells in the cervix, and a similar number had detectable responses in blood. Where both blood and cervical responses were detected in the same individual, the specificity of the responses was similar. Neither cervical nor blood responses were detected in lower-risk control donors. HIV-specific CD8+ T cell frequencies in the cervix of HIV-resistant sex workers were slightly higher than in blood, while in HIV-infected donor cervical response frequencies were markedly lower than blood, so that there was relative enrichment of cervical responses in HIV-resistant compared with HIV-infected donors. HIV-specific CD8+ T cell responses in the absence of detectable HIV infection in the genital mucosa of HIV-1-resistant sex workers may be playing an important part in protective immunity against heterosexual HIV-1 transmission.

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“…In fact, it has been estimated that the total number of Ig-secreting B cells in the gut LP of mice accounts for more than 80% of all plasma B cells in the body [28]. One study found no depletion of Ig-secreting B cells in HIV-infected men [1], but there was a depletion of plasma B cells in HIV-infected women [59]. It still needs to be determined whether plasma B cells are in fact selectively lost in HIV infection.…”

Section: Estimates For Ielsmentioning

confidence: 99%

“…Being part of the innate immune system, loss of CD4-expressing gut macrophages and DCs can impair the ability of B and T lymphocytes to mount immune responses. Several studies have found no reduction in the number of macrophages and loss of DCs in HIV-infected patients [59][60][61]. More studies are needed to determine which types of DCs are lost in HIV infection.…”

Section: Estimates For Ielsmentioning

confidence: 99%