title: Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype.
abstract: Antiretroviral therapy (ART) induces rapid suppression of viral replication and a progressive replenishment of CD4(+) T cells in HIV-infected individuals. However, the effect of ART on restoring pre-existing memory CD4(+) T cells specific for common copathogens is still unclear. To better understand the dynamics of Ag-specific CD4(+) T cells during ART, we assessed the frequency, functional capacity, and memory profile of CD4(+) T cells specific for Mycobacterium tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART initiation. After ART initiation, the frequency of M. tuberculosis-specific CD4(+) T cells showed little change, whereas CMV-specific CD4(+) T cells were significantly lower (p = 0.003). There was no difference in the polyfunctional or memory profile of Ag-specific CD4(+) T cells before and after ART. The replenishment of Ag-specific CD4(+) T cells correlated with the memory differentiation profile of these cells prior to ART. Pathogen-specific CD4(+) T cells exhibiting a late differentiated profile (CD45RO(+)CD27(-)) had a lower capacity to replenish (p = 0.019; r = -0.5) compared with cells with an early differentiated profile (CD45RO(+)CD27(+); p = 0.04; r = 0.45). In conclusion, restoration of copathogen-specific memory CD4(+) T cells during treated HIV infection is related to their memory phenotype, in which early differentiated cells (such as most M. tuberculosis-specific cells) have a higher replenishment capacity compared with late differentiated cells (such as most CMV-specific cells). These data identify an important, hitherto unrecognized, factor that may limit restoration of copathogen immunity in HIV-infected individuals on ART.
authors.affiliation: Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.affiliation: Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Ramla F
authors.initials: RF
authors.lastname: Tanko
authors.affiliation: Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Andreia P
authors.initials: AP
authors.lastname: Soares
authors.affiliation: Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Lindi
authors.initials: L
authors.lastname: Masson
authors.affiliation: Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.affiliation: Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Garrett
authors.affiliation: Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Natasha
authors.initials: N
authors.lastname: Samsunder
authors.affiliation: Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Quarraisha Abdool
authors.initials: QA
authors.lastname: Karim
authors.affiliation: Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Salim S Abdool
authors.initials: SSA
authors.lastname: Karim
authors.affiliation: Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Burgers
mesh_terms: D044966:Anti-Retroviral Agents / Q000276:immunology* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D019562:Viral Load / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens