Progressive impairment of monocytic function in HIV-1-infected human macrophage hybridomas.
Using human macrophage hybridomas infected with HIV-1, we investigated monocyte function over a 5-week period after HIV-1 infection. Two clones, 63 and 30, were infected with HIV-1IIIB. Infection was documented by RT activity (15 x 10(6) cpm/ml), intracytoplasmic staining with an anti-p24 antibody, in situ hybridization with an HIV-1-specific riboprobe, and electron microscopy showing intracytoplasmic virus. Two weeks after infection, clones 63 and 30 lost expression of all class II antigens (DR, 81.7 vs. 0%; DQ, 15.6 vs. 0%; and DP, 76.9 vs. 0%) while retaining expression of class I (87.4 vs. 84.1%), LFA-1 (82.4 vs. 83.1%), and LFA-3 (79.1 vs. 74.7%) antigens when compared to uninfected cells. When tested for functional integrity, infected but not uninfected clone 63 cells failed to stimulate a tetanus-specific MHC-restricted T cell proliferative response 2 weeks after infection. Cytokine secretion and antigen processing were also perturbed as production of IL-1 was abolished 2 weeks after infection (although IL-6 secretion was augmented) and infected clone 63 cells failed to process exogenous antigen. Last, the viability of T cells cocultured with infected clone 63 was dramatically decreased 35 days after infection (85 vs. 15%). There was no evidence of transmission of HIV-1 to T cells, suggesting a toxic effect of infected clone 63. Taken together, these data suggest that altered macrophage function in our system occurs at multiple levels, which may account for the early immunological defects described in HIV-1 infection.
Sperber
K
K
Division of Clinical Immunology, Mount Sinai Medical Center, New York, New York 10029.
Hamrang
G
G
Louie
M J
MJ
Kalb
T
T
Banerjee
R
R
Choi
H S
HS
Paronetto
F
F
Mayer
L
L
D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000382:microbiology; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D013745:Tetanus Toxoid / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015850:Interleukin-6; D016169:Lymphocyte Function-Associated Antigen-1; D013745:Tetanus Toxoid