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Dysregulation of CD28 and CTLA-4 expression by CD4 T cells from previously immunodeficient HIV-infected patients with sustained virological responses to highly active antiretroviral therapy.
HIV Med. 2005 Jul; 6(4):278-83.HM

Abstract

OBJECTIVES

Current guidelines recommend commencing highly active antiretroviral therapy (HAART) in HIV-infected patients when CD4 T-cell counts reach 350 cells/microL. However, late-presenting HIV-infected patients with CD4 T-cell counts<50 cells/microL are still common. The ability of long-term HAART to normalize immune dysregulation in severely immunodeficient HIV-infected patients remains unclear. Here we address indices of immune dysregulation in previously severely immunocompromised HIV-infected patients treated with long-term HAART who had achieved increased CD4 T-cell counts and complete suppression of HIV viraemia.

METHODS

We examined expression of CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and intracellular perforin by CD4 and CD8 lymphocytes from 25 highly selected HIV-infected patients [nadir CD4 T-cell counts <50 cells/microL, >4 years on HAART and >6 months of complete viral suppression (<50 HIV-1 RNA copies/mL)] and 18 HIV-seronegative age- and sex-matched controls.

RESULTS

HIV-infected patients had lower percentages of CD28-expressing CD4 lymphocytes and higher percentages of CTLA-4-expressing CD4 lymphocytes than controls. The percentage of CTLA-4-expressing CD4 lymphocytes correlated inversely with that of CD28-expressing CD4 lymphocytes. The proportion of CD4 lymphocytes expressing perforin was generally low. However, more HIV-infected patients than controls had >1% of CD4 lymphocytes expressing perforin [11 of 25 (44%) vs. one of 18 (5.5%)]. The percentage of CD8 lymphocytes expressing perforin did not differ between HIV-infected patients and controls. Amongst HIV-infected patients, the percentage of perforin-expressing CD8 lymphocytes correlated inversely with nadir but not current CD4 T-cell count.

CONCLUSIONS

Expression of CD28, CTLA-4 and perforin by CD4 lymphocytes remain dysregulated in HIV-infected patients with previous severe immunodeficiency, despite increased CD4 T-cell counts and control of HIV viraemia by HAART.

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Authors+Show Affiliations

Stone SF
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital and School of Surgery and Pathology, University of Western Australia, Perth, Australia. sfstone@graduate.uwa.edu.au
Price P
No affiliation info available
French MA
No affiliation info available

MeSH

Antigens, CDAntigens, DifferentiationAntiretroviral Therapy, Highly ActiveCD28 AntigensCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCTLA-4 AntigenHIV InfectionsHumansImmunosuppressive AgentsMembrane GlycoproteinsPerforinPhenotypePore Forming Cytotoxic ProteinsViral Load

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16011533

Citation

Stone, S F., et al. "Dysregulation of CD28 and CTLA-4 Expression By CD4 T Cells From Previously Immunodeficient HIV-infected Patients With Sustained Virological Responses to Highly Active Antiretroviral Therapy." HIV Medicine, vol. 6, no. 4, 2005, pp. 278-83.
Stone SF, Price P, French MA. Dysregulation of CD28 and CTLA-4 expression by CD4 T cells from previously immunodeficient HIV-infected patients with sustained virological responses to highly active antiretroviral therapy. HIV Med. 2005;6(4):278-83.
Stone, S. F., Price, P., & French, M. A. (2005). Dysregulation of CD28 and CTLA-4 expression by CD4 T cells from previously immunodeficient HIV-infected patients with sustained virological responses to highly active antiretroviral therapy. HIV Medicine, 6(4), 278-83.
Stone SF, Price P, French MA. Dysregulation of CD28 and CTLA-4 Expression By CD4 T Cells From Previously Immunodeficient HIV-infected Patients With Sustained Virological Responses to Highly Active Antiretroviral Therapy. HIV Med. 2005;6(4):278-83. PubMed PMID: 16011533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulation of CD28 and CTLA-4 expression by CD4 T cells from previously immunodeficient HIV-infected patients with sustained virological responses to highly active antiretroviral therapy. AU - Stone,S F, AU - Price,P, AU - French,M A, PY - 2005/7/14/pubmed PY - 2006/3/8/medline PY - 2005/7/14/entrez SP - 278 EP - 83 JF - HIV medicine JO - HIV Med VL - 6 IS - 4 N2 - OBJECTIVES: Current guidelines recommend commencing highly active antiretroviral therapy (HAART) in HIV-infected patients when CD4 T-cell counts reach 350 cells/microL. However, late-presenting HIV-infected patients with CD4 T-cell counts<50 cells/microL are still common. The ability of long-term HAART to normalize immune dysregulation in severely immunodeficient HIV-infected patients remains unclear. Here we address indices of immune dysregulation in previously severely immunocompromised HIV-infected patients treated with long-term HAART who had achieved increased CD4 T-cell counts and complete suppression of HIV viraemia. METHODS: We examined expression of CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and intracellular perforin by CD4 and CD8 lymphocytes from 25 highly selected HIV-infected patients [nadir CD4 T-cell counts <50 cells/microL, >4 years on HAART and >6 months of complete viral suppression (<50 HIV-1 RNA copies/mL)] and 18 HIV-seronegative age- and sex-matched controls. RESULTS: HIV-infected patients had lower percentages of CD28-expressing CD4 lymphocytes and higher percentages of CTLA-4-expressing CD4 lymphocytes than controls. The percentage of CTLA-4-expressing CD4 lymphocytes correlated inversely with that of CD28-expressing CD4 lymphocytes. The proportion of CD4 lymphocytes expressing perforin was generally low. However, more HIV-infected patients than controls had >1% of CD4 lymphocytes expressing perforin [11 of 25 (44%) vs. one of 18 (5.5%)]. The percentage of CD8 lymphocytes expressing perforin did not differ between HIV-infected patients and controls. Amongst HIV-infected patients, the percentage of perforin-expressing CD8 lymphocytes correlated inversely with nadir but not current CD4 T-cell count. CONCLUSIONS: Expression of CD28, CTLA-4 and perforin by CD4 lymphocytes remain dysregulated in HIV-infected patients with previous severe immunodeficiency, despite increased CD4 T-cell counts and control of HIV viraemia by HAART. SN - 1464-2662 UR - https://www.unboundmedicine.com/medline/citation/16011533/Dysregulation_of_CD28_and_CTLA_4_expression_by_CD4_T_cells_from_previously_immunodeficient_HIV_infected_patients_with_sustained_virological_responses_to_highly_active_antiretroviral_therapy_ L2 - https://doi.org/10.1111/j.1468-1293.2005.00307.x DB - PRIME DP - Unbound Medicine ER -