Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.

Rowland‐Jones, Sarah; Dong, Tao; Fowke, Keith R.; Kimani, Joshua; Krausa, P.; Newell, Helen; Blanchard, Tom; Ariyoshi, Koya; Oyugi, Julius; Ngugi, Elizabeth; Bwayo, Job J.; MacDonald, Kelly S.; Mcmichael, A. J.; Plummer, Francis A.

doi:10.1172/jci4314

Cited by 370 publications

(174 citation statements)

References 40 publications

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“…These mechanisms are the focus of studies of why some individuals who are exposed to known risk factors, do not develop mental health problems. This approach has provided insights into resilience in the same way that somatic studies have investigated commercial sex workers who have not contracted HIV/AIDS (Rowland-Jones et al, 1998;Kaul, Plummer, Kimani, Dong, Kiama, & Rostron, 2000), or cancer survivors who have exceeded their life expectancies (Gotay, Isaacs, & Pagano, 2004). In the mental health domain such ‗high-exposure' studies have included patients awaiting cardiac surgery with resilience to anxiety-related heart rate hyperactivation (Bokeriia, Golukhova, Polunina, Davydov, & Kruglova, 2008), people after bereavement with resilience to chronic grief (Bonanno et al, 2002), and other examples of individuals retaining a positive outlook in difficult circumstances (Felten & Hall, 2001;Windle, Markland & Woods, 2008;Jones, 2006;Becoña, 2007).…”

Section: A Biopsychosocial (Multi-level) Construct For Mental Resiliencementioning

confidence: 99%

Resilience and mental health

Davydov¹,

Stewart²,

Ritchie

et al. 2010

Clinical Psychology Review

937

729

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Section: A Biopsychosocial (Multi-level) Construct For Mental Resiliencementioning

confidence: 99%

Resilience and mental health

Davydov¹,

Stewart²,

Ritchie

et al. 2010

Clinical Psychology Review

937

729

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“…This may be partly due to the difficulties inherent in demonstrating low-frequency CTL using samples obtained from a site with a rich microbial flora and that contain relatively few T lymphocytes. The IFN-␥ enzymelinked immunospot (ELISPOT) assay, which has been previously used to document HIV-specific CD8 ϩ responses in the blood of both HIV-1-infected and HEPS donors (15,21), provides an estimate of Ag-specific CD8 ϩ lymphocyte frequencies that correlates closely with those measured by either tetrameric MHC-peptide complexes or limiting dilution CTL assays (22). ELISPOT offers the added advantages of being an overnight assay, thereby minimizing the effect of bacterial contamination, and of requiring fewer input cells than standard bulk CTL assays (15,22,23).…”

Section: T Is Now Recognized That There Is Variability In Susceptibmentioning

confidence: 99%

“…It is estimated that these women have over 60 unprotected sexual exposures to HIV-1 per year, despite behavioral counseling and provision of condoms; their exposure is uniformly through vaginal intercourse. Resistance in this subgroup is associated with systemic HIV-1-specific Th and CTLs (7,15), mucosal HIV-1-specific IgA responses (7), and certain MHC class I/II alleles (27), but not with polymorphisms in CCR5 or altered cellular susceptibility to HIV-1 (3). We now report the occurrence and specificity of HIV-1-specific, IFN-␥-secreting, CD8 ϩ T lymphocytes in both cervix and blood of these HIV-1-resistant sex workers.…”

Section: T Is Now Recognized That There Is Variability In Susceptibmentioning

confidence: 99%

“…Epitope selection was based on 1) the class I HLA haplotype of the donor; and 2) where possible, on the results of previous systemic HIV-1-specific CTL assays in this study population (15). Peptides were synthesized by F-moc chemistry using a Zinnser Analytical synthesizer (Advanced Chemtech, Louisville, KY), and purity was established by HPLC.…”

Section: Hiv-1 Ctl Epitope Selection and Peptide Synthesismentioning

confidence: 99%

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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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“…Tentative evidence for this is provided by the study of exposed but uninfected Kenian sex workers, who seemed to be protected from the virus, possibly through frequent exposure to the HIV virus which would boost the immune response (Rowland-Jones et al, 1998). It should be noted that a number of these women seroconverted after they reduced their sexual activity, confirming the idea that continuous boosting might be necessary to confer protection (Kaul et al, 2001).…”

Section: Discussionmentioning

confidence: 95%

Contrasting B cell- and T cell-based protective vaccines

Jansen

Altes

Funk

et al. 2005

Journal of Theoretical Biology

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A substantial research effort is devoted to the development of vaccines based on T cells. Such a vaccine would provide a means to protect against infection with HIV and stop the current pandemic. Here we investigate the possibility to develop a protective T cellbased vaccine. We do this by means of a mathematical model which describes the dynamics of a pathogen and the immune system in the early stages of infection. We compare an immune response that is near immediate-as is the case for a humoral response-with that of a response in which the effector cells have to be formed from precursor cells-as occurs in T cell responses. The latter applies to a T cell-based vaccine. A near immediate response is associated with a threshold number of effector cells above which an infection cannot take hold. For a T cell-based vaccine this threshold increases with the amount of antigen the immune system is exposed to. For small initial doses, as one would naturally expect to occur, this gives rise to impractically large thresholds. Thus, although a T cell vaccine might work against a high dose exposure, it might fail when exposed against to a low-dose exposure. This limits, we argue, the efficacy of T cell-based vaccines. r

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Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.

Cited by 370 publications

References 40 publications

Resilience and mental health

Resilience and mental health

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

Contrasting B cell- and T cell-based protective vaccines

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