B cell-driven HIV type 1 expression in T cells: an essential role of CD86 costimulatory molecule.
During HIV-1 infection, HIV-1 is sequestered and actively replicates within lymphoid organs, mainly in areas essential for antigen-specific T-B interactions. We investigated whether cognate T-B interactions not only drive humoral response to HIV-1 but also enhance viral replication. Costimulation of in vitro HIV-1-infected tonsillar T cells with autologous or allogeneic activated B cells increased both viral replication and T cell proliferation. Addition of CD86 MAb to cocultures inhibited most p24 (84 +/- 12%, n = 13) and IL-2 (99 +/- 2%, n = 6) production, decreased T cell proliferation by 46 +/- 15% (n = 13), and decreased TNF-alpha and IFN-gamma production by 67 +/- 17% (n = 6) and 53 +/- 6% (n = 6), respectively. In contrast, CD80 MAb, which strongly inhibited IL-2 production (77 +/- 10%, n = 6), moderately downregulated p24 and TNF-alpha production (29 +/- 21%, n = 13 and 34 +/- 10%, n = 6, respectively) and did not decrease T cell proliferation (8 +/- 10%, n = 13) or IFN-gamma production (14 +/- 13%, n = 6). We thus showed that B cells deliver a potent CD86/CD28 costimulatory signal that induces T cell proliferation and simultaneously enhances HIV-1 replication. CD86+ B cells, mainly localized within the light zone of germinal centers, might thus favor active in situ replication of HIV-1 in response to each new challenge by T-dependent antigens.
INSERM U131, Institut Paris-Sud sur les Cytokines, Clamart, France.
R
R
Krzysiek
E A
EA
Lefèvre
C
C
Legendre
D
D
Treton
D
D
Dormont
P
P
Galanaud
G
G
Gras
Y
Y
Richard
D015703:Antigens, CD / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014779:Virus Replication
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins