Interferon-Gamma Responses to Candida Recover Slowly or Remain Low in Immunodeficient HIV Patients Responding to ART
| Autor: | Niamh M. Keane, Martyn A. French, John R. Warmington, Kate Burgess, Shelley F. Stone, Ian James, Patricia Price, Andrew Y. F. Lim |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Cart Antigens Fungal T-Lymphocytes Immunology Enolase Cytomegalovirus HIV Infections Viremia Biology Peripheral blood mononuclear cell Interferon-gamma Antigen medicine Humans Immunology and Allergy Interferon gamma IL-2 receptor Antigens Viral Cellular Senescence Aged Candida ELISPOT virus diseases Middle Aged medicine.disease Virology Anti-Retroviral Agents Phosphopyruvate Hydratase Cytomegalovirus Infections HIV-1 RNA Viral medicine.drug |
| Zdroj: | Journal of Clinical Immunology. 26:160-167 |
| ISSN: | 1573-2592 0271-9142 |
| Popis: | Extended assessments of memory T-cell responses in HIV patients who have a satisfactory virological response to combination antiretroviral therapy (CART) have been limited by availability of longitudinal samples and of antigens to which most individuals (including HIV-negative controls) have been exposed. Studies of cytomegalovirus (CMV) show that interferon-gamma (IFN-gamma) responses never recover completely, but this may be antigen-specific. Here we present responses to Candida and CMV antigens analyzed using a statistical approach that derives overall trends from samples collected at variable time points. Results were considered in relation to putative markers of T-regulatory cells. Blood mononuclear cells collected from seventeen HIV-1 patients (nadir100 CD4 T cells/mL) 0-8 years after initiation of CART were stimulated with Candida spp lysate, Candida enolase protein or CMV lysate and production of IFN-gamma was assessed by ELISpot assay. CD4 T-cell counts increased fivefold and stabilized within 24 months on CART, following control of plasma viremia. IFN-gamma responses to Candida antigens began low and increased slowly, generating positive slope up to 60 months on CART (Candida enolase p=0.008; Candida lysate p=0.03; mixed-model Wald test). Only two patients displayed a CMV or Candida-specific IFN-gamma response above the median for seronegative controls. Proportions of T cells expressing CD25 or CD57 did not correlate with IFN-gamma responses. Slow reconstitution of IFN-gamma responses to CMV and Candida in previously immunodeficient patients with restored CD4+ T-cell counts on CART suggests a broad and nonresolving defect in memory T-cell responses. |
| Databáze: | OpenAIRE |
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