Pathogen-specific induction of CD154 is impaired in CD4+ T cells from human immunodeficiency virus-infected patients.
The pathogenesis of immunodeficiency associated with human immunodeficiency virus (HIV) infection remains incompletely understood. CD154, a molecule that is expressed primarily on activated CD4(+) T cells, is pivotal for regulation of cell-mediated and humoral immunity and is crucial for control of many opportunistic infections. We investigated whether CD4(+) T cells from HIV-infected patients exhibit defective induction of CD154 in response to opportunistic pathogens. Incubation of purified human CD4(+) T cells with monocytes plus antigenic preparations of either Candida albicans, cytomegalovirus, or Toxoplasma gondii resulted in induction of CD154. Expression of CD154 in response to these pathogens was impaired in CD4(+) T cells from HIV-infected patients. This defect correlated with decreased production of interleukin (IL)-12 and interferon (IFN)-gamma in response to T. gondii. Recombinant CD154 partially restored secretion of IL-12 and IFN-gamma in response to T. gondii in cells from HIV-infected patients. Together, defective induction of CD154 is likely to contribute to impaired cell-mediated immunity against opportunistic pathogens in HIV-infected patients.
Subauste
Carlos S
CS
Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. carlos.subauste@uc.edu
Wessendarp
Matthew
M
Portilllo
Jose-Andres C
JA
Andrade
Rosa M
RM
Hinds
Linda M
LM
Gomez
Francisco J
FJ
Smulian
A George
AG
Grubbs
Peter A
PA
Haglund
Lisa A
LA
D017088:AIDS-Related Opportunistic Infections / Q000209:etiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D000946:Antigens, Fungal / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D037181:Lectins, C-Type; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014122:Toxoplasma / Q000276:immunology / Q000472:pathogenicity; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000946:Antigens, Fungal; D000953:Antigens, Protozoan; D023201:CD40 Ligand; D007371:Interferon-gamma; D018664:Interleukin-12; D037181:Lectins, C-Type; D011994:Recombinant Proteins; D000099192:CD69 Antigens