Increased extrafollicular expression of the B-cell stimulatory molecule CD70 in HIV-1-infected individuals.
OBJECTIVE
CD70 molecules expressed by activated T cells provide potent B cell stimulatory signals. We hypothesized that an altered CD70 expression might contribute to B cell abnormalities during HIV-1 infection.


METHODS
CD70 expression and the functional and migratory properties of the CD4CD70 T lymphocytes were analyzed in HIV-1-infected patients and in humanized mice. Correlations were tested between CD70 expression and features of B-cell activation, apoptosis sensitivity and functional exhaustion.


METHODS
CD4CD70 T cells were analyzed in cohorts of CD4 T-cell lymphopenic, viremic or nonlymphopenic, nonviremic HIV-1-infected patients and in noninfected individuals. CD70 upregulation was also followed in HIV-1-infected humanized mice. CD38, CD95, LAIR1 and PD-1 expressions were monitored on B-cell subpopulations, Ki67 was assessed to estimate B-cell proliferation and antibody levels were measured in plasma.


RESULTS
Blood CD4CD70 T-cell frequencies increased in response to CD4 T-cell depletion or high viremia levels as a possible consequence of increased activation and proliferation in this subset. CD4CD70 T cells produced T-helper 1-type cytokines and expressed chemokine receptors mobilizing toward sites of inflammation but not to lymphoid follicles. High CD70 expression was observed in HIV-1-infected humanized mice at extrafollicular sites (peritoneum, bone-marrow). CD4CD70 T-cell frequencies correlated with the expression of the activation marker CD38 and the death receptor CD95 on various memory B-cell subsets, with B-cell proliferation and with plasma IgG levels.


CONCLUSIONS
CD4CD70 T cells may contribute to B cell hyperactivation and accelerated memory B-cell turnover during HIV-1 infection.
aDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden bDynamics of Immune Responses, Division of Immunology, San Raffaele Scientific Institute, Milan, Italy cLaboratory of Retrovirology, Department of infection and immunity, Luxembourg Institute of Health, Luxembourg dImmunology and Infectious Diseases, GIGA-Signal Transduction, University of Liège, Liege, Belgium eDepartment of Infectious Diseases/Venhälsan, South General Hospital, Stockholm, Sweden.
Rebecka
R
Lantto
Aikaterini
A
Nasi
Stefano
S
Sammicheli
Sylvie
S
Amu
Virginie
V
Fievez
Michel
M
Moutschen
Simone
S
Pensieroso
Bo
B
Hejdeman
Francesca
F
Chiodi
Bence
B
Rethi
D000328:Adult; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D053282:CD27 Ligand / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000032:analysis; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged
D000954:Antigens, Surface; D053282:CD27 Ligand; C505771:CD70 protein, human; D015483:HIV Antibodies; D019394:Ki-67 Antigen