Human Immunodeficiency Virus-Specific CD8<sup>+</sup>T Cells in Human Breast Milk

Sabbaj, Steffanie; Edwards, Bradley H.; Ghosh, Mrinal K.; Semrau, Katherine; Cheelo, Sanford; Thea, Donald M.; Kuhn, Louise; Ritter, Gerd; Mulligan, Mark J.; Goepfert, Paul; Aldrovandi, Grace M.

doi:10.1128/jvi.76.15.7365-7373.2002

Cited by 58 publications

(54 citation statements)

References 56 publications

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“…All displayed increased frequency of tetramer binding T cells in breast milk when compared with PBMC (Table I). This is consistent with our prior studies wherein we found that the tetramer frequency in blood was only 0.22% compared with 0.65% in breast milk (12).…”

Section: Ag-specific Ifn-␥-secreting Cd8supporting

confidence: 82%

“…Milk samples were kept at 4°C for no Ͼ5 h and then milk was centrifuged at 400 ϫ g for 15 min. Cream that formed at the top was scooped out with a sterile spatula, milk supernatant was saved for viral load determinations, and the cell pellet was washed two times with HBSS (12). Cells were resuspended in complete RPMI 1640 with 10% AB sera and viable BMC were counted using a hemocytometer by trypan blue exclusion.…”

Section: Isolation Of Breast Milk Cellsmentioning

confidence: 99%

“…An IFN-␥ ELISPOT assay was used to enumerate HIV-specific T cells from breast milk or PBMC of HIV-infected or uninfected women (12). Briefly, 96-well nitrocellulose plates (Milliliter HA; Millipore) were coated with 5 g/ml mouse anti-human IFN-␥ mAb (clone 1-D1K; Mabtech) and then incubated overnight at 4°C.…”

Section: Ifn-␥ Elispot Assaymentioning

confidence: 99%

“…Furthermore, even when these tissues are available for study, the number of Ag-specific T cells obtained is too small to adequately evaluate. Recently, we and others (11,12) demonstrated the presence of Ag-specific CD8 ϩ T cells in breast milk of HIV-positive women. These cells were present in relatively large numbers and were readily available from women agreeing to donate breast milk postpartum.…”

mentioning

confidence: 99%

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Breast Milk-Derived Antigen-Specific CD8+ T Cells: An Extralymphoid Effector Memory Cell Population in Humans

Sabbaj

Ghosh

Edwards

et al. 2005

The Journal of Immunology

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Although mouse studies have demonstrated the presence of an effector memory population in nonlymphoid tissues, the phenotype of human CD8+ T cells present in such compartments has not been characterized. Because of the relatively large number of CD8+ T cells present in breast milk, we were able to characterize the phenotype of this cell population in HIV-infected and uninfected lactating women. CMV, influenza virus, EBV, and HIV-specific CD8+ T cells as measured by the IFN-γ ELISPOT and MHC class I tetramer staining were all present at greater frequencies in breast milk as compared with blood. Furthermore, a greater percentage of the breast milk CD8+ T cells expressed the intestinal homing receptor, CD103, and the mucosal homing receptor CCR9. Breast milk T cells were predominantly CD45RO+HLADR+ and expressed low levels of CD45RA, CD62L, and CCR7 consistent with an effector memory population. Conversely, T cells derived from blood were mainly characterized as central memory cells (CCR7+CD62L+). These results demonstrate a population of extralymphoid CD8+ T cells with an effector memory phenotype in humans, which could contribute to enhanced local virologic control and the relative lack of HIV transmission via this route.

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Section: Ag-specific Ifn-␥-secreting Cd8supporting

confidence: 82%

Section: Isolation Of Breast Milk Cellsmentioning

confidence: 99%

Section: Ifn-␥ Elispot Assaymentioning

confidence: 99%

mentioning

confidence: 99%

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Breast Milk-Derived Antigen-Specific CD8+ T Cells: An Extralymphoid Effector Memory Cell Population in Humans

Sabbaj

Ghosh

Edwards

et al. 2005

The Journal of Immunology

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“…[40][41][42] A specific oligosaccharide epitope in breast milk, Lewis X component, was recently discovered to be able to bind to dendritic cell-specific ICAM3-grabbing nonintegrin (DC-SIGN), thereby inhibiting HIV transfer to CD4 cells. 43 Further study of other breast milk parameters, including of HIV-specific cellular immune responses 44,45 and innate immune factors, remains important to further understanding of how to make breast-feeding safer. …”

Section: Discussionmentioning

confidence: 99%

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Kuhn

Trabattoni

Kankasa

et al. 2006

The Journal of Pediatrics

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Objectives-To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants.Study design-Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters).Results-HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities.Conclusions-HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants.Human immunodeficiency virus (HIV) can be transmitted from an HIV-infected mother to her child through breast-feeding. This poses a serious dilemma for health policy-makers. Although complete avoidance of breast-feeding would eliminate the risk of breast-feeding-associated transmission, breast milk substitutes are unaffordable, unavailable, unacceptable, and unsafe for many HIV-infected women in low resource settings. The quantity of viral RNA and cellassociated viral DNA in breast milk from HIV-positive women strongly predicts mother-tochild transmission among breast-fed infants. [1][2][3] What is puzzling, however, is why the majority of breast-fed infants born to HIV-positive mothers remain uninfected despite prolonged exposure. Although breast milk is clearly a route of transmission, human milk is also a rich source of a multitude of innate and specific immune factors that may play a role in modulating the risk of infection. 4 Better understanding of anti-infective properties of breast milk may assist Secretory immunoglobulin A (sIgA) is the predominant immunoglobulin in breast milk and is associated with passive immunity to other (non-HIV) pathogens among breast-fed infants. 5 HIV-specific IgA antibodies are detected in breast milk of a high proportion of HIV-positive, lactating women. [6][7][8] In an in vitro model, sIgA purified from colostrum was able to block one of the pathways involved in HIV penetration across mucosa, that is, transcytosis through epithelial cells, 9 suggesting that sIgA may be related to decreased infectivity of breast milk. Although persistence of HIV-specific IgA and IgM in breast milk was associated with reduced transmission in one study in Rwanda, 10 no protective association was observed in two other studies. 8,11 HIV-specific sIgA has been detected frequently in cervicovaginal samples from exposed but persistently uninfected cohorts of high-risk women, 12-14 suggesting a role for these mucosal responses in resistance to HIV. Purified sIgA from ex...

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Biological mechanisms of vertical human immunodeficiency virus (HIV‐1) transmission

Lehman

Farquhar

2007

Reviews in Medical Virology

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In the absence of interventions, 30-45% of exposed infants acquire human immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission. It remains unclear why some infants become infected while others do not, despite significant exposure to HIV-1 in utero, during delivery and while breastfeeding. Here we discuss the correlates of vertical transmission with an emphasis on factors that increase maternal HIV-1 levels, either systemically or locally in genital secretions and breast milk. Immune responses may influence maternal viral load, and data suggest that maternal neutralising antibodies reduce infection rates. In addition, infants may be capable of mounting HIV-specific cellular immune responses. We propose that both humoral and cellular responses are necessary to reduce infection because cell-free as well as cell-associated virus appears to play a role in vertical transmission. These distinct forms of the virus may be targeted most effectively by different components of the immune system. We also discuss the use of antiretrovirals to reduce transmission, focusing on the mechanisms of action of regimens currently used in developing country settings. We conclude that prevention relies not only on reducing maternal HIV-1 levels within blood, genital tract and breast milk, but also on pre- and/or post-exposure prophylaxis to the infant. However, HIV-1 has the capacity to mutate under drug pressure and rapidly acquires mutations conferring antiretroviral resistance. This review concludes with data on persistence of low-level resistance after delivery as well as recent guidelines for maternal and infant regimens designed to limit resistance.

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Human Immunodeficiency Virus-Specific CD8⁺T Cells in Human Breast Milk

Cited by 58 publications

References 56 publications

Breast Milk-Derived Antigen-Specific CD8+ T Cells: An Extralymphoid Effector Memory Cell Population in Humans

Breast Milk-Derived Antigen-Specific CD8+ T Cells: An Extralymphoid Effector Memory Cell Population in Humans

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Biological mechanisms of vertical human immunodeficiency virus (HIV‐1) transmission

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Human Immunodeficiency Virus-Specific CD8+T Cells in Human Breast Milk

Cited by 58 publications

References 56 publications

Breast Milk-Derived Antigen-Specific CD8+ T Cells: An Extralymphoid Effector Memory Cell Population in Humans

Breast Milk-Derived Antigen-Specific CD8+ T Cells: An Extralymphoid Effector Memory Cell Population in Humans

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Biological mechanisms of vertical human immunodeficiency virus (HIV‐1) transmission

Contact Info

Product

Resources

About

Human Immunodeficiency Virus-Specific CD8⁺T Cells in Human Breast Milk