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Jeffrey Pido-Lopez

Publications and source records attributed to Jeffrey Pido-Lopez.

9 recordsLinked to original sources
PubMed2004

Reversal of thymic atrophy.

Age-associated thymic atrophy is a key event preceding the inefficient functioning of the immune system, resulting in a diminished capacity to generate new T-cells. This thymic involution has been proposed to be due to changes in the thymic microenvironment resulting in its failure to support thymopoiesis. A key cytokine in the early stages of thymocyte development is IL-7 and expression levels are greatly reduced with age. The ability of IL-7 to restore the immune system by enhancing thymic output remains controversial. In this review, we highlight the advances in molecular approaches used to evaluate recent thymic emigrants and assess the success of these strategies in determining whether IL-7 can lead to immune reconstitution.

Aging↗
PubMed2004

Improved thymic function in exclusively breastfed infants is associated with higher interleukin 7 concentrations in their mothers' breast milk.

BACKGROUND: In rural Gambians, the season of birth strongly predicts adult mortality. Those born during the harvest season have longer life spans than do those born during the hungry season, and the deaths associated with infectious diseases suggest permanent early-life influences on immunity. Thymic measurements showed significantly smaller thymuses in infants born during the hungry season than in those born during the harvest season. The differences were greatest at 8 wk of age, a time when all infants were exclusively breastfed, which suggests the involvement of breast milk factors. OBJECTIVE: This study tested whether thymic size differences reflect thymic output and ascertained whether thymic output is associated with breast milk interleukin 7 (IL-7) concentrations. DESIGN: We studied thymic size and output in a prospective cohort of 138 Gambian infants born in either the hungry or the harvest season by measuring signal-joint T cell receptor-rearrangement excision circles (sjTRECs) at birth and at 8 wk of age. IL-7 concentrations in breast milk were measured by using an enzyme-linked immunosorbent assay. RESULTS: By age 8 wk, those born in the hungry season had significantly lower sjTREC counts than did those born in the harvest season (0.97 and 2.12 sjTRECs/100 T cells, respectively; P = 0.006). At 1 wk postpartum, the breast milk of mothers of infants born in the hungry season had significantly lower IL-7 than did that of mothers of infants born in the harvest season (79 and 100 pg/mL, respectively; P = 0.02). The findings were similar at 8 wk postpartum. CONCLUSION: These data show a plausible pathway linking external seasonal insults to mothers with thymic development in their infants, which suggests possible implications for long-term programming of immunity.

Breast Feeding↗
PubMed2004

Interleukin-7: an interleukin for rejuvenating the immune system.

Infection of an individual (aged 20-30 years) by a virus will cause a response from the T (thymus derived) lymphocytes of which there are approximately 3 x 10(11). If the individual has not met the virus before, the response will come from the naive T cell subset (50 +/- 10% of the total T cell pool at this age) containing recent thymic emigrants produced from the thymus at approximately 10(8) per day. Their antigen-specific receptor has a defined specificity governed by the conformation of its two chains (alpha and beta), and the repertoire of specificities is somewhere in the region of 2 x 10(7) to 10(8). A successful response leads to clonal expansion and the generation of memory T cells to the infecting agent.

Adult↗
PubMed2004

Enhanced T-cell maturation, differentiation and function in HIV-1-infected individuals after growth hormone and highly active antiretroviral therapy.

BACKGROUND: Strong virus-specific helper and cytotoxic T-cell responses correlate with non-progression during HIV-1 infection. Administration of antiretroviral therapy (ART) during the chronic phases of HIV-1 infection fails to restore these responses in most patients. DESIGN AND METHODS: We assessed the changes in immune function of 12 HIV-1-positive individuals treated with ART for over 4 years, who received 4 mg/day of recombinant human growth hormone (rhGH) for 12 weeks and were then randomized into groups receiving either placebo, twice weekly or alternate day dosing of rhGH. Peripheral blood was drawn for phenotypic analysis and functional assays at time points 0, 12 and 24 weeks. RESULTS: At week 12, we observed significant increases in naive CD4 T cells (P<0.01) and effector CD8 T cells based on CD45RA and CCR7 expression (P<0.02). In addition, we observed a rise in HIV-1 antigen-specific CD4 (P<0.005) and CD8 (P<0.05) T-cell responses. Twelve weeks post-randomization into placebo, alternate day or twice weekly dosing (24 weeks post-baseline), the phenotype and function of the virus-specific effector CD8 T cells seen at week 12 was maintained in most patients regardless of randomization arm and despite the disappearance of HIV-1-specific CD4 T-cell responses. CONCLUSIONS: Concomitant administration of rhGH at 4 mg/day with highly active ART appears to partially reverse some of the defects exerted on the immune system by HIV-1. This combination may represent a valuable immunotherapeutic intervention aiding in the treatment of chronic HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Thymic output during initial highly active antiretroviral therapy (HAART) and during HAART supplementation with interleukin 2 and/or with HIV type 1 immunogen (Remune).

The thymic output of patients receiving highly active antiretroviral therapy (HAART) was assessed by sjTREC (signal joint T cell receptor rearrangement excision circle) analysis to determine the thymic contribution to CD4(+) T cell reconstitution during initial therapy and during interleukin 2 (IL-2) and/or Remune supplementation of HAART. Levels of sjTRECs were observed to decline dramatically after the first 4 weeks of HAART and then increased without significant associated changes in CD4(+) T cell counts. HAART supplementation with IL-2 was observed to lead to rapid increases in CD4(+) T cells that were accompanied by sjTREC decreases. No notable changes in CD4(+) T cell counts and sjTRECs were seen in patients receiving HAART supplemented with Remune alone. The results indicate CD4(+) T cell maintenance during initial treatment of HIV-1 with HAART and early CD4(+) T cell reconstitution of patients receiving IL-2 with HAART is largely due to thymus-independent mechanisms, with the thymus making a limited contribution.

AIDS Vaccines↗
PubMed2002

Molecular quantitation of thymic output in mice and the effect of IL-7.

Aging of the murine thymus is accompanied by a measurable loss of weight and cellularity and a marked reduction in its output of T lymphocytes. This study employs a molecular approach to determine changes in the output of the murine thymus using a novel assay system based on the detection and quantitation of the excised TCRdelta DNA locus from within the TCRalpha chain genes. In alpha beta(+) T cells such delta excision circles (deltaEC) are present at higher levels in naive T cells as compared with memory T cell populations, are non-replicating, and diluted within the total peripheral alpha beta(+) T cell pool with advancing age. This assay permits the assessment of thymic output in older animals where previous analysis was hampered by the transient nature of the naive T cell surface phenotype, and so allows the assessment of the efficacy of IL-7 as an agent to reverse thymic atrophy. Treatment of old mice with IL-7 although producing no overall change in the total number of alpha beta(+) T cells in the peripheral T cell pool altered the component subsets. Mice treated with IL-7 showed increases in the number of alpha beta(+)TCR cells possessing deltaEC commensurate with improved thymic output, and the splenic T cells from IL-7-treated mice performed significantly better in in vitro functional assays compared to those from age-matched saline-treated controls.

Aging↗
PubMed2002

Immune reconstitution in HIV-1-infected patients.

HIV-1-specific CD8 cytotoxic and CD4 helper T-lymphocytes, which are respectively the central effector and regulatory cells in viral infections, together with fully functional antigen-presenting cells, are essential at all stages of HIV-1 infection to control viral activity. Recent studies indicate that such protective HIV-1-specific immune responses can be preserved/induced in HIV-1-infected individuals, utilizing strategies such as treatment interruption after early HAART. Despite successful combination antiretroviral drug therapy, strong anti-HIV-1 T-cell responses are often not apparent in chronic HIV-1 infection, diminishing the probability of viral eradication. Thus, the therapeutic use of immunization and cytokines are required to induce and steer immunity towards a desirable outcome. Here, we review and discuss therapeutic immunization and immunotherapy with regard to their potential use in the treatment of chronic HIV-1 infection.

AIDS Vaccines↗