Deleterious effect of HIV-1 plasma viremia on B cell costimulatory function.
HIV infection leads to numerous immunologic defects, including impaired B cell function. An effective humoral response requires bidirectional interactions between B cells and CD4(+) T cells, critical of which are interactions between CD80/CD86 expressed on activated B cells and CD28 expressed on responder CD4(+) T cells. In the present study, we examined the effect of active HIV replication on B cell costimulatory function. Induction of CD80/CD86 on B cells following B cell receptor and CD40 triggering and responsiveness of CD4(+) T cells to activated B cells were investigated in a system where B cells of HIV-infected patients were compared concurrently to B cells of HIV-negative donors. In contrast to HIV-aviremic patients, B cells of HIV-viremic patients were ineffective at stimulating CD4(+) T cells, as measured by the induction of activation markers and proliferation. The importance of interactions of CD80/CD86 and CD28 in activating CD4(+) T cells was clear; the ablation of a normal response following the addition of neutralizing anti-CD86/CD80 Abs mirrored the response of CD4(+) T cells to B cells of HIV-viremic patients, while the addition of exogenous CD28 ligands partially restored the poor CD4(+) T cell response to the B cells of HIV-viremic patients. Ineffective B cell costimulatory function in HIV-viremic patients was associated with low induction of CD80/CD86 expression on B cells. Our findings further delineate the scope of defects associated with cognate B cell-CD4(+) T cell interactions in HIV infection and suggest that therapeutic interventions designed to enhance CD28-dependent costimulatory pathways may help restore immune functions.
Malaspina
Angela
A
Department of Health and Human Services, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Moir
Susan
S
Kottilil
Shyamasundaran
S
Hallahan
Claire W
CW
Ehler
Linda A
LA
Liu
Shuying
S
Planta
Marie A
MA
Chun
Tae-Wook
TW
Fauci
Anthony S
AS
D015703:Antigens, CD / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D019013:CD40 Antigens / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D015536:Down-Regulation / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D012367:RNA, Viral / Q000097:blood; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D011947:Receptors, Antigen, B-Cell