Mechanism of B and T cell death during HIV infection

The work of our group aims at understanding the mechanisms of cell damage during HIV infection.

Several cell types are damaged during the infection, through the direct effect of the virus and through indirect mechanisms of damage. In fact B lymphocytes which are not the direct targets for the infection, are severely impaired in number and function during HIV infection. The mechanisms underlying such dysfunctions are poorly understood but other mechanisms in addition to direct virus replication account for deletion of immune cells including T and B cells.

We and other groups have shown that T and B cells from infected subjects are primed for apoptosis. The expression of Fas and FasL (pivotal molecules in the regulation of apoptosis) is increased, indicating that this receptor-ligand pair may play a crucial role for loss of immune cells. One crucial question is the characterization of the molecular pathway leading to up-regulation of Fas and FasL during HIV infection. The expression of these molecules is increased on B and T cells in blood from the early stages of infection, already at the time of primary infection.

We found that memory B cells are lost in infected patients, likely due to terminal differentiation of memory B cells to plasma cells. The effector function of B cells is also impaired during HIV infection in that we found a decline of antibodies to previously met antigens either during childhood or through vaccination. Also, a limited amount of neutralizing antibodies, aimed at controlling virus infection, is produced in HIV infected subjects who progress to AIDS.

We believe that the understanding of the mechanisms leading to cell damage during AIDS may be important to design future anti-HIV therapies and vaccines. Studies which we conduct on additional groups of immunocompromised patients may help to through light on the mechanism of T and B cell depletion during HIV infection.

Project Groups within the Francesca Chiodi

Maria Issagouliantis

Britta Wahren

Group members


Former Group Members


Sven Grützmeier, Ander Karlsson and Bo Heideman

The Gay Men's Health Clinic, South Hospital, Stockholm and Ann Atlas. Department of Medicine at Solna, Infectious Disease Unit. Clinical collaborator on several studies These doctors scientists are colloborating with us on issues of immunological relevance for AIDS.


Streptococcus pneumoniae Nasopharyngeal Carriage among PCV-10-Vaccinated HIV-1-Infected Children with Maintained Serological Memory in Ethiopia.
Lemma M, Bekele Y, Petkov S, Hägglund M, Petros B, Aseffa A, et al
Pathogens 2020 Feb;9(3):

Early antiretroviral therapy may preserve vaccine responses in HIV infected patients by preventing damage to long-lived plasma cells.
Nilsson A, Chiodi F
J. Infect. Dis. 2019 Dec;():

Impact of chemokine C-C ligand 27, foreskin anatomy and sexually transmitted infections on HIV-1 target cell availability in adolescent South African males.
Gray CM, O'Hagan KL, Lorenzo-Redondo R, Olivier AJ, Amu S, Chigorimbo-Murefu N, et al
Mucosal Immunol 2020 01;13(1):118-127

Defining characteristics of genital health in South African adolescent girls and young women at high risk for HIV infection.
Dabee S, Barnabas S, Lennard K, Jaumdally S, Gamieldien H, Balle C, et al
PLoS ONE 2019 ;14(4):e0213975

Homing defects of B cells in HIV-1 infected children impair vaccination responses.
Bekele Y, Lemma M, Bobosha K, Yibeltal D, Nasi A, Gebre M, et al
Vaccine 2019 Apr;37(17):2348-2355

Mass cytometry identifies distinct CD4+ T cell clusters distinguishing HIV-1-infected patients according to antiretroviral therapy initiation.
Bekele Y, Lakshmikanth T, Chen Y, Mikes J, Nasi A, Petkov S, et al
JCI Insight 2019 Feb;4(3):

DNA immunization site determines the level of gene expression and the magnitude, but not the type of the induced immune response.
Petkov S, Starodubova E, Latanova A, Kilpeläinen A, Latyshev O, Svirskis S, et al
PLoS ONE 2018 ;13(6):e0197902

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity.
Latanova A, Petkov S, Kilpelainen A, Jansons J, Latyshev O, Kuzmenko Y, et al
Sci Rep 2018 May;8(1):8078

Converging epidemics of sexually transmitted infections and bacterial vaginosis in southern African female adolescents at risk of HIV.
Barnabas S, Dabee S, Passmore J, Jaspan H, Lewis D, Jaumdally S, et al
Int J STD AIDS 2018 05;29(6):531-539

Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?
Bekele Y, Graham R, Soeria-Atmadja S, Nasi A, Zazzi M, Vicenti I, et al
Front Immunol 2017 ;8():1966

Mechanisms regulating expansion of CD8+ T cells during HIV-1 infection.
Nasi A, Chiodi F
J. Intern. Med. 2018 Mar;283(3):257-267

T follicular helper cells and antibody response to Hepatitis B virus vaccine in HIV-1 infected children receiving ART.
Bekele Y, Yibeltal D, Bobosha K, Andargie T, Lemma M, Gebre M, et al
Sci Rep 2017 08;7(1):8956

IL-7 and CD4 T Follicular Helper Cells in HIV-1 Infection.
Chiodi F, Bekele Y, Lantto Graham R, Nasi A
Front Immunol 2017 ;8():451

Dendritic Cell Response to HIV-1 Is Controlled by Differentiation Programs in the Cells and Strain-Specific Properties of the Virus.
Nasi A, Amu S, Göthlin M, Jansson M, Nagy N, Chiodi F, et al
Front Immunol 2017 ;8():244

Impaired B cells survival upon production of inflammatory cytokines by HIV-1 exposed follicular dendritic cells.
Sabri F, Prados A, Muñoz-Fernández R, Lantto R, Fernandez-Rubio P, Nasi A, et al
Retrovirology 2016 09;13(1):61

Pneumococcal vaccination of HIV-infected young adults is an important global priority.
Chiodi F
AIDS 2016 07;30(12):1991-3

Dysfunctional phenotypes of CD4+ and CD8+ T cells are comparable in patients initiating ART during early or chronic HIV-1 infection.
Amu S, Lantto Graham R, Bekele Y, Nasi A, Bengtsson C, Rethi B, et al
Medicine (Baltimore) 2016 Jun;95(23):e3738

Increased extrafollicular expression of the B-cell stimulatory molecule CD70 in HIV-1-infected individuals.
Lantto R, Nasi A, Sammicheli S, Amu S, Fievez V, Moutschen M, et al
AIDS 2015 Sep;29(14):1757-66

Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART.
Bekele Y, Amu S, Bobosha K, Lantto R, Nilsson A, Endale B, et al
Medicine (Baltimore) 2015 Jul;94(27):e1125

Frequency and phenotype of B cell subpopulations in young and aged HIV-1 infected patients receiving ART.
Amu S, Lavy-Shahaf G, Cagigi A, Hejdeman B, Nozza S, Lopalco L, et al
Retrovirology 2014 Sep;11():76

B-cell responses after intranasal vaccination with the novel attenuated Bordetella pertussis vaccine strain BPZE1 in a randomized phase I clinical trial.
Jahnmatz M, Amu S, Ljungman M, Wehlin L, Chiodi F, Mielcarek N, et al
Vaccine 2014 Jun;32(27):3350-6

Combined efforts in immunology and vaccinology will lead to effective vaccines against HIV, tuberculosis and malaria.
Chiodi F, Kaufmann S
J. Intern. Med. 2014 May;275(5):442-3

Human immunodeficiency virus antibodies and the vaccine problem.
Chiodi F, Weiss R
J. Intern. Med. 2014 May;275(5):444-55

Toll-like receptor 3 signalling up-regulates expression of the HIV co-receptor G-protein coupled receptor 15 on human CD4+ T cells.
Kiene M, Rethi B, Jansson M, Dillon S, Lee E, Lantto R, et al
PLoS ONE 2014 ;9(2):e88195

Impairment of B-cell functions during HIV-1 infection.
Amu S, Ruffin N, Rethi B, Chiodi F
AIDS 2013 Sep;27(15):2323-34

Relation of activation-induced deaminase (AID) expression with antibody response to A(H1N1)pdm09 vaccination in HIV-1 infected patients.
Cagigi A, Pensieroso S, Ruffin N, Sammicheli S, Thorstensson R, Pan-Hammarström Q, et al
Vaccine 2013 Apr;31(18):2231-7

B-cell subset alterations and correlated factors in HIV-1 infection.
Pensieroso S, Galli L, Nozza S, Ruffin N, Castagna A, Tambussi G, et al
AIDS 2013 May;27(8):1209-17

Concerted effect of lymphopenia, viraemia and T-cell activation on Fas expression of peripheral B cells in HIV-1-infected patients.
Rethi B, Sammicheli S, Amu S, Pensieroso S, Hejdeman B, Schepis D, et al
AIDS 2013 Jan;27(2):155-62

The role of the alternative coreceptor GPR15 in SIV tropism for human cells.
Kiene M, Marzi A, Urbanczyk A, Bertram S, Fisch T, Nehlmeier I, et al
Virology 2012 Nov;433(1):73-84

Reduction of HIV-1 load in semen during follow-up study of RV144 vaccine trial boosts interest for novel correlates of immune protection in genital mucosa.
Spetz A, Chiodi F
J. Infect. Dis. 2013 Apr;207(8):1189-92

Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection.
Ruffin N, Lantto R, Pensieroso S, Sammicheli S, Hejdeman B, Rethi B, et al
J. Intern. Med. 2012 Nov;272(5):492-503

Soluble CD27 induces IgG production through activation of antigen-primed B cells.
Dang L, Nilsson A, Ingelman-Sundberg H, Cagigi A, Gelinck L, Titanji K, et al
J. Intern. Med. 2012 Mar;271(3):282-93

IL-7 modulates B cells survival and activation by inducing BAFF and CD70 expression in T cells.
Sammicheli S, Ruffin N, Lantto R, Vivar N, Chiodi F, Rethi B
J. Autoimmun. 2012 Jun;38(4):304-14

Short communication: phylogenetic characterization of HIV type 1 CRF01_AE V3 envelope sequences in pregnant women in Northern Vietnam.
Caridha R, Ha T, Gaseitsiwe S, Hung P, Anh N, Bao N, et al
AIDS Res. Hum. Retroviruses 2012 Aug;28(8):852-6

Towards a world free from HIV and AIDS?
Albert J, Chiodi F
J. Intern. Med. 2011 Dec;270(6):502-8

Survival and proliferation of CD28- T cells during HIV-1 infection relate to the amplitude of viral replication.
Vivar N, Ruffin N, Sammicheli S, Hejdeman B, Rethi B, Chiodi F
J. Infect. Dis. 2011 Jun;203(11):1658-67

The involvement of epithelial Fas in a human model of graft versus host disease.
Ruffin N, Ahmed S, Osorio L, Wang X, Jackson G, Collin M, et al
Transplantation 2011 May;91(9):946-51

Role of Fas/FasL in regulation of inflammation in vaginal tissue during HSV-2 infection.
Krzyzowska M, Shestakov A, Eriksson K, Chiodi F
Cell Death Dis 2011 Mar;2():e132

The involvement of epithelial Fas in a human model of graft versus host disease.
Ruffin N, Ahmed S, Osorio L, Wang X, Jackson G, Collin M, et al
Transplantation 2011 May;91(9):946-51

Measles outbreak in Africa--is there a link to the HIV-1 epidemic?
Nilsson A, Chiodi F
PLoS Pathog. 2011 Feb;7(2):e1001241

New therapy to revert dysfunctional antibody responses during HIV-1 infection.
Chiodi F
J. Clin. Invest. 2010 Nov;120(11):3810-3

The role of IL-1beta in reduced IL-7 production by stromal and epithelial cells: a model for impaired T-cell numbers in the gut during HIV-1 infection.
Thang P, Ruffin N, Brodin D, Rethi B, Cam P, Hien N, et al
J. Intern. Med. 2010 Aug;268(2):181-93

Dysfunctional B-cell responses during HIV-1 infection: implication for influenza vaccination and highly active antiretroviral therapy.
Cagigi A, Nilsson A, Pensieroso S, Chiodi F
Lancet Infect Dis 2010 Jul;10(7):499-503

The impact of active HIV-1 replication on the physiological age-related decline of immature-transitional B-cells in HIV-1 infected children.
Cagigi A, Palma P, Nilsson A, Di Cesare S, Pensieroso S, Kakoulidou M, et al
AIDS 2010 Aug;24(13):2075-80

Impact of gamma-chain cytokines on T cell homeostasis in HIV-1 infection: therapeutic implications.
Gougeon M, Chiodi F
J. Intern. Med. 2010 May;267(5):502-14


Mailing address

Department of Microbiology, Tumor and Cell Biology
Karolinska Institutet
SE–171 77 Stockholm

Visiting address

Department of Microbiology, Tumor and Cell Biology
Solnavägen 9, floor 9, Quarter 9C

Content reviewer:
Sara Lidman