Characteristics of lymphocyte subsets in HIV-infected, long-term nonprogressor, and healthy Asian children through 12 years of age
Jintanat Ananworanich, Tanakorn Apornpong, Pope Kosalaraksa, Tanyathip Jaimulwong, Rawiwan Hansudewechakul, Chitsanu Pancharoen, Torsak Bunupuradah, Mom Chandara, Thanyawee Puthanakit, Chaiwat Ngampiyasakul, Jurai Wongsawat, Suparat Kanjanavanit, Wicharn Luesomboon, Phennapha Klangsinsirikul, Nicole Ngo-Giang-Huong, Stephen J Kerr, Sasiwimol Ubolyam, Tawan Mengthaisong, Rebecca S Gelman, Kovit Pattanapanyasat, Vonthanak Saphonn, Kiat Ruxrungtham, William T Shearer, PREDICT Study Group, P Phanuphak, K Ruxrungtham, M C Vun, V Saphonn, J Kaldor, D A Cooper, K Chokephaibulkit, V Sirisanthana, P Suntarattiwong, M Cotton, C Giaquinto, R Lolekha, L Fox, A Ojumu, J E Bupp, N Weatherall, M Ussery, L M Mofenson, P Brouwers, W T Shearer, V G Valcour, R Paul, K Pattanapanyasat, N Sakulploy, J M McNicholl, K Ruxrungtham, J Ananworanich, T Puthanakit, C Thanee, A Klinklom, C Pancharoen, T Bunupuradah, S J Kerr, J van der Lugt, T Chuenyam, S Ubolyam, A Mahanontharit, T Suwanlerk, J Intasan, T Jupimai, P Intakan, T Hirunyanulux, C Sriheara, A Uanithirat, P Boonrak, O Rit-im, C Phadungphon, W Thongsee, O Chaiya, T Sattong, K Nantapisan, A Piromwong, N Kuljarusiri, S Aryukarn, S Sripanom, N Naknoi, S Muangtokit, S Kumkrung, P Chaemsai, J Wongsawat, R Sunthornkachit, V Moolasart, N Siripongpreeda, S Thongyen, P Chathaisong, V Prommool, D Suwannamass, S Waradejwinyoo, N Boonyarittipat, T Chiewcharn, S Likanonsakul, C Athichathana, B Eampokalap, W Sanchiem, P Kosalaraksa, P Lumbiganon, C Engchanil, P Tharnprisan, C Sopharak, V Lulitanond, S Khahmahpahte, R Kaewmart, P Chaimanee, M Sala, T Udompanit, R Wisai, S Rattanamanee, Y Chantarasuk, S Sarvok, Y Changtrakun, S Kunhasura, S Kamollert, W Luesomboon, P Eiamapichart, T Jadwattanakul, I Limpet-ngam, D Naraporn, P Mathajittiphun, C Sirimaskul, W Klaihong, P Sittisak, T Wongwian, K Charoenthammachoke, P Yodpo, S Kanjanavanit, M Ananthanavanich, P Sornchai, T Namwong, D Chutima, S Tangmankhongworakun, P Yingyong, J Kasinrerk, M Raksasang, P Kongdong, S Khampangkome, S Thong-Ngao, S Paengta, K Junsom, R Khuankaew, P Moolsombat, D Khuttiwung, C Chanrin, R Hansudewechakul, Y Jariyapongpaiboon, C Chanta, A Khonponoi, C Yodsuwan, W Srisuk, P Ussawawuthipong, Y Thaweesombat, P Tongsuk, C Kumluang, R Jinasen, N Maneerat, K Surapanichadul, P Donkaew, S Vonthanak, U Vibol, S Sophan, P Boren, K Chettra, L Phary, T Roeun, T Sunly, M Chandara, C Sokheng, K Sokoeun, T Sotharin, S Vonthanak, U Vibol, V Bun, S C Meng, K Chettra, S Phan, W I Vong, K Dyna, C Ngampiyasakul, N Srisawat, W Chamjamrat, S Wattanayothin, P Prasertphan, T Wongcheeree, P Greetanukroh, C Imubumroong, P Teirsonsern, Jintanat Ananworanich, Tanakorn Apornpong, Pope Kosalaraksa, Tanyathip Jaimulwong, Rawiwan Hansudewechakul, Chitsanu Pancharoen, Torsak Bunupuradah, Mom Chandara, Thanyawee Puthanakit, Chaiwat Ngampiyasakul, Jurai Wongsawat, Suparat Kanjanavanit, Wicharn Luesomboon, Phennapha Klangsinsirikul, Nicole Ngo-Giang-Huong, Stephen J Kerr, Sasiwimol Ubolyam, Tawan Mengthaisong, Rebecca S Gelman, Kovit Pattanapanyasat, Vonthanak Saphonn, Kiat Ruxrungtham, William T Shearer, PREDICT Study Group, P Phanuphak, K Ruxrungtham, M C Vun, V Saphonn, J Kaldor, D A Cooper, K Chokephaibulkit, V Sirisanthana, P Suntarattiwong, M Cotton, C Giaquinto, R Lolekha, L Fox, A Ojumu, J E Bupp, N Weatherall, M Ussery, L M Mofenson, P Brouwers, W T Shearer, V G Valcour, R Paul, K Pattanapanyasat, N Sakulploy, J M McNicholl, K Ruxrungtham, J Ananworanich, T Puthanakit, C Thanee, A Klinklom, C Pancharoen, T Bunupuradah, S J Kerr, J van der Lugt, T Chuenyam, S Ubolyam, A Mahanontharit, T Suwanlerk, J Intasan, T Jupimai, P Intakan, T Hirunyanulux, C Sriheara, A Uanithirat, P Boonrak, O Rit-im, C Phadungphon, W Thongsee, O Chaiya, T Sattong, K Nantapisan, A Piromwong, N Kuljarusiri, S Aryukarn, S Sripanom, N Naknoi, S Muangtokit, S Kumkrung, P Chaemsai, J Wongsawat, R Sunthornkachit, V Moolasart, N Siripongpreeda, S Thongyen, P Chathaisong, V Prommool, D Suwannamass, S Waradejwinyoo, N Boonyarittipat, T Chiewcharn, S Likanonsakul, C Athichathana, B Eampokalap, W Sanchiem, P Kosalaraksa, P Lumbiganon, C Engchanil, P Tharnprisan, C Sopharak, V Lulitanond, S Khahmahpahte, R Kaewmart, P Chaimanee, M Sala, T Udompanit, R Wisai, S Rattanamanee, Y Chantarasuk, S Sarvok, Y Changtrakun, S Kunhasura, S Kamollert, W Luesomboon, P Eiamapichart, T Jadwattanakul, I Limpet-ngam, D Naraporn, P Mathajittiphun, C Sirimaskul, W Klaihong, P Sittisak, T Wongwian, K Charoenthammachoke, P Yodpo, S Kanjanavanit, M Ananthanavanich, P Sornchai, T Namwong, D Chutima, S Tangmankhongworakun, P Yingyong, J Kasinrerk, M Raksasang, P Kongdong, S Khampangkome, S Thong-Ngao, S Paengta, K Junsom, R Khuankaew, P Moolsombat, D Khuttiwung, C Chanrin, R Hansudewechakul, Y Jariyapongpaiboon, C Chanta, A Khonponoi, C Yodsuwan, W Srisuk, P Ussawawuthipong, Y Thaweesombat, P Tongsuk, C Kumluang, R Jinasen, N Maneerat, K Surapanichadul, P Donkaew, S Vonthanak, U Vibol, S Sophan, P Boren, K Chettra, L Phary, T Roeun, T Sunly, M Chandara, C Sokheng, K Sokoeun, T Sotharin, S Vonthanak, U Vibol, V Bun, S C Meng, K Chettra, S Phan, W I Vong, K Dyna, C Ngampiyasakul, N Srisawat, W Chamjamrat, S Wattanayothin, P Prasertphan, T Wongcheeree, P Greetanukroh, C Imubumroong, P Teirsonsern
Abstract
Background: There are limited data on the immune profiles of HIV-positive children compared with healthy controls, and no such data for Asian children.
Objectives: To immunophenotype HIV-positive Asian children, including long-term nonprogressors (LTNPs), compared with age-matched healthy controls.
Methods: We used flow cytometry to analyze 13 lymphocyte and monocyte subsets from 222 untreated, HIV-positive children with 15% to 24% CD4(+) T cells and no AIDS-related illnesses and 142 healthy children (controls). Data were compared among age categories. Profiles from LTNPs (n = 50), defined as children ≥8 years old with CD4(+) T-cell counts ≥350 cells/mm(3), were compared with data from age-matched non-LTNPs (n = 17) and controls (n = 53).
Results: Compared with controls, HIV-positive children had lower values (cell count per mm(3) and percent distribution) for T(H) cells and higher values for cytotoxic T cells, with reductions in populations of naive T(H) and cytotoxic T cells, B cells, and natural killer (NK) cells. HIV-positive children had high values for activated T(H) and cytotoxic T cells. Compared with non-LTNPs, LTNPs had higher values of T(H) and cytotoxic T cells, naive and memory T-cell subsets, and B and NK cells. Surprisingly, counts of activated T(H) and cytotoxic T cells were also higher among LTNPs. LNTPs were more frequently male.
Conclusion: Untreated, HIV-infected Asian children have immune profiles that differ from those of controls, characterized by low values for T(H) cells, naive T cells, B cells, and NK cells but high values for cytotoxic, activated T(H), and cytotoxic T cells. The higher values for activated T cells observed in LTNPs require confirmation in longitudinal studies.
Trial registration: ClinicalTrials.gov NCT00234091.
Conflict of interest statement
Conflict of interest: Authors declare no conflict of interest
Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Figures
![Figures 1A to 1E. Comparison of cell…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3004741/bin/nihms247491f1a.jpg)
Figures 1A to 1E. Comparison of cell…
Figures 1A to 1E. Comparison of cell subsets among 4 age groups of HIV-negative and…
Figures 1A to 1E. Comparison of cell…
Figures 1A to 1E. Comparison of cell subsets among 4 age groups of HIV-negative and…
- Lymphocyte subsets in healthy Malawians: implications for immunologic assessment of HIV infection in Africa.Mandala WL, MacLennan JM, Gondwe EN, Ward SA, Molyneux ME, MacLennan CA. Mandala WL, et al. J Allergy Clin Immunol. 2010 Jan;125(1):203-8. doi: 10.1016/j.jaci.2009.10.010. Epub 2009 Nov 26. J Allergy Clin Immunol. 2010. PMID: 19944455 Free PMC article.
- Distinct phenotype of unrestricted cytotoxic T lymphocytes from human immunodeficiency virus-infected individuals.Parsons MS, Zipperlen K, Gallant M, Howley C, Grant M. Parsons MS, et al. J Clin Immunol. 2010 Mar;30(2):272-9. doi: 10.1007/s10875-009-9361-1. Epub 2010 Jan 23. J Clin Immunol. 2010. PMID: 20099013
- Naïve CD4+ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.Xu L, Liu Y, Song X, Li Y, Han Y, Zhu T, Cao W, Li T. Xu L, et al. BMC Immunol. 2021 Jun 3;22(1):36. doi: 10.1186/s12865-021-00426-8. BMC Immunol. 2021. PMID: 34082709 Free PMC article.
- Increased monocyte activation with age among HIV-infected long term non-progressor children: implications for early treatment initiation.D'Souza RR, Gopalan BP, Rajnala N, Phetsouphanh C, Shet A. D'Souza RR, et al. HIV Med. 2019 Sep;20(8):513-522. doi: 10.1111/hiv.12751. Epub 2019 May 26. HIV Med. 2019. PMID: 31131542
- Immunoregulatory T cells may be involved in preserving CD4 T cell counts in HIV-infected long-term nonprogressors and controllers.Gaardbo JC, Ronit A, Hartling HJ, Gjerdrum LM, Springborg K, Ralfkiær E, Thorsteinsson K, Ullum H, Andersen ÅB, Nielsen SD. Gaardbo JC, et al. J Acquir Immune Defic Syndr. 2014 Jan 1;65(1):10-8. doi: 10.1097/QAI.0b013e3182a7c932. J Acquir Immune Defic Syndr. 2014. PMID: 23995946
- Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.Vieira VA, Herbert N, Cromhout G, Adland E, Goulder P. Vieira VA, et al. Front Immunol. 2022 May 11;13:886562. doi: 10.3389/fimmu.2022.886562. eCollection 2022. Front Immunol. 2022. PMID: 35634290 Free PMC article. Review.
- Two Distinct Mechanisms Leading to Loss of Virological Control in the Rare Group of Antiretroviral Therapy-Naive, Transiently Aviremic Children Living with HIV.Vieira VA, Adland E, Grayson NE, Csala A, Richards F, Dacon C, Athavale R, Tsai MH, D'Souza R, Muenchhoff M, Bonsall D, Jooste P, Goulder PJR. Vieira VA, et al. J Virol. 2022 Jan 26;96(2):e0153521. doi: 10.1128/JVI.01535-21. Epub 2021 Nov 10. J Virol. 2022. PMID: 34757843 Free PMC article.
- Variation of B cell subsets with age in healthy Malawians.Mandala WL, Longwe H. Mandala WL, et al. PLoS One. 2021 Jul 9;16(7):e0254320. doi: 10.1371/journal.pone.0254320. eCollection 2021. PLoS One. 2021. PMID: 34242324 Free PMC article.
- Increased Regulatory T-Cell Activity and Enhanced T-Cell Homeostatic Signaling in Slow Progressing HIV-infected Children.Roider J, Ngoepe A, Muenchhoff M, Adland E, Groll A, Ndung'u T, Kløverpris H, Goulder P, Leslie A. Roider J, et al. Front Immunol. 2019 Feb 12;10:213. doi: 10.3389/fimmu.2019.00213. eCollection 2019. Front Immunol. 2019. PMID: 30809229 Free PMC article.
- HIV-1 Subtype C-Infected Children with Exceptional Neutralization Breadth Exhibit Polyclonal Responses Targeting Known Epitopes.Ditse Z, Muenchhoff M, Adland E, Jooste P, Goulder P, Moore PL, Morris L. Ditse Z, et al. J Virol. 2018 Aug 16;92(17):e00878-18. doi: 10.1128/JVI.00878-18. Print 2018 Sep 1. J Virol. 2018. PMID: 29950423 Free PMC article.
- Clinical Trial
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Asia
- Cell Separation
- Child
- Child, Preschool
- Disease Progression
- Female
- Flow Cytometry
- HIV / immunology*
- HIV / pathogenicity
- HIV Infections / epidemiology
- HIV Infections / immunology*
- HIV Infections / pathology
- HIV Infections / physiopathology
- Humans
- Immunophenotyping*
- Lymphocyte Activation
- Male
- T-Lymphocyte Subsets / immunology
- T-Lymphocyte Subsets / metabolism*
- T-Lymphocyte Subsets / pathology
- T-Lymphocyte Subsets / virology
- T-Lymphocytes, Cytotoxic / immunology
- T-Lymphocytes, Cytotoxic / metabolism*
- T-Lymphocytes, Cytotoxic / pathology
- T-Lymphocytes, Cytotoxic / virology
- ClinicalTrials.gov/NCT00234091
- Full Text Sources
- Medical
- Research Materials
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![Figures 1A to 1E. Comparison of cell…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3004741/bin/nihms247491f1b.jpg)
Figures 1A to 1E. Comparison of cell…
Figures 1A to 1E. Comparison of cell subsets among 4 age groups of HIV-negative and…
- Lymphocyte subsets in healthy Malawians: implications for immunologic assessment of HIV infection in Africa.Mandala WL, MacLennan JM, Gondwe EN, Ward SA, Molyneux ME, MacLennan CA. Mandala WL, et al. J Allergy Clin Immunol. 2010 Jan;125(1):203-8. doi: 10.1016/j.jaci.2009.10.010. Epub 2009 Nov 26. J Allergy Clin Immunol. 2010. PMID: 19944455 Free PMC article.
- Distinct phenotype of unrestricted cytotoxic T lymphocytes from human immunodeficiency virus-infected individuals.Parsons MS, Zipperlen K, Gallant M, Howley C, Grant M. Parsons MS, et al. J Clin Immunol. 2010 Mar;30(2):272-9. doi: 10.1007/s10875-009-9361-1. Epub 2010 Jan 23. J Clin Immunol. 2010. PMID: 20099013
- Naïve CD4+ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.Xu L, Liu Y, Song X, Li Y, Han Y, Zhu T, Cao W, Li T. Xu L, et al. BMC Immunol. 2021 Jun 3;22(1):36. doi: 10.1186/s12865-021-00426-8. BMC Immunol. 2021. PMID: 34082709 Free PMC article.
- Increased monocyte activation with age among HIV-infected long term non-progressor children: implications for early treatment initiation.D'Souza RR, Gopalan BP, Rajnala N, Phetsouphanh C, Shet A. D'Souza RR, et al. HIV Med. 2019 Sep;20(8):513-522. doi: 10.1111/hiv.12751. Epub 2019 May 26. HIV Med. 2019. PMID: 31131542
- Immunoregulatory T cells may be involved in preserving CD4 T cell counts in HIV-infected long-term nonprogressors and controllers.Gaardbo JC, Ronit A, Hartling HJ, Gjerdrum LM, Springborg K, Ralfkiær E, Thorsteinsson K, Ullum H, Andersen ÅB, Nielsen SD. Gaardbo JC, et al. J Acquir Immune Defic Syndr. 2014 Jan 1;65(1):10-8. doi: 10.1097/QAI.0b013e3182a7c932. J Acquir Immune Defic Syndr. 2014. PMID: 23995946
- Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.Vieira VA, Herbert N, Cromhout G, Adland E, Goulder P. Vieira VA, et al. Front Immunol. 2022 May 11;13:886562. doi: 10.3389/fimmu.2022.886562. eCollection 2022. Front Immunol. 2022. PMID: 35634290 Free PMC article. Review.
- Two Distinct Mechanisms Leading to Loss of Virological Control in the Rare Group of Antiretroviral Therapy-Naive, Transiently Aviremic Children Living with HIV.Vieira VA, Adland E, Grayson NE, Csala A, Richards F, Dacon C, Athavale R, Tsai MH, D'Souza R, Muenchhoff M, Bonsall D, Jooste P, Goulder PJR. Vieira VA, et al. J Virol. 2022 Jan 26;96(2):e0153521. doi: 10.1128/JVI.01535-21. Epub 2021 Nov 10. J Virol. 2022. PMID: 34757843 Free PMC article.
- Variation of B cell subsets with age in healthy Malawians.Mandala WL, Longwe H. Mandala WL, et al. PLoS One. 2021 Jul 9;16(7):e0254320. doi: 10.1371/journal.pone.0254320. eCollection 2021. PLoS One. 2021. PMID: 34242324 Free PMC article.
- Increased Regulatory T-Cell Activity and Enhanced T-Cell Homeostatic Signaling in Slow Progressing HIV-infected Children.Roider J, Ngoepe A, Muenchhoff M, Adland E, Groll A, Ndung'u T, Kløverpris H, Goulder P, Leslie A. Roider J, et al. Front Immunol. 2019 Feb 12;10:213. doi: 10.3389/fimmu.2019.00213. eCollection 2019. Front Immunol. 2019. PMID: 30809229 Free PMC article.
- HIV-1 Subtype C-Infected Children with Exceptional Neutralization Breadth Exhibit Polyclonal Responses Targeting Known Epitopes.Ditse Z, Muenchhoff M, Adland E, Jooste P, Goulder P, Moore PL, Morris L. Ditse Z, et al. J Virol. 2018 Aug 16;92(17):e00878-18. doi: 10.1128/JVI.00878-18. Print 2018 Sep 1. J Virol. 2018. PMID: 29950423 Free PMC article.
- Clinical Trial
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Asia
- Cell Separation
- Child
- Child, Preschool
- Disease Progression
- Female
- Flow Cytometry
- HIV / immunology*
- HIV / pathogenicity
- HIV Infections / epidemiology
- HIV Infections / immunology*
- HIV Infections / pathology
- HIV Infections / physiopathology
- Humans
- Immunophenotyping*
- Lymphocyte Activation
- Male
- T-Lymphocyte Subsets / immunology
- T-Lymphocyte Subsets / metabolism*
- T-Lymphocyte Subsets / pathology
- T-Lymphocyte Subsets / virology
- T-Lymphocytes, Cytotoxic / immunology
- T-Lymphocytes, Cytotoxic / metabolism*
- T-Lymphocytes, Cytotoxic / pathology
- T-Lymphocytes, Cytotoxic / virology
- ClinicalTrials.gov/NCT00234091
- Full Text Sources
- Medical
- Research Materials
![Figures 1A to 1E. Comparison of cell…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3004741/bin/nihms247491f1c.jpg)
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