title: Type 1 and type 2 cytokines in HIV infection -- a possible role in apoptosis and disease progression.
abstract: The progression of HIV-infected subjects to AIDS was recently postulated to be controlled by the balance between type 1 cytokines (mainly enhancing cell-mediated immunity) and type 2 cytokines (mainly augmenting antibody production). Thus, progression of HIV infection was suggested to be accompanied by a decline of in vitro production of interleukin-2 (IL-2), IL-12 and interferon gamma (IFN-gamma) (type 1 cytokines) and an increase in the production of IL-4, IL-5, IL-6 and IL-10 (type 2 cytokines) by peripheral blood mononuclear cells of HIV-seropositive patients. According to this hypothesis, clinical markers of progression would be considered the loss of the ability to elicit a delayed-type hypersensitivity reaction to ubiquitous antigens (secondary to defective IL-2 production), hyper-IgE (secondary to increased IL-4 production) and hypereosynophilia (secondary to increased IL-5 production). The type 1 to type 2 shift was suggested to be predictive for the following events: (i) reduction in CD4 counts; (ii) time to AIDS diagnosis; (iii) time to death. Support for this hypothesis stems from the recent observation that a strong type 1/weak type 2 cytokine production profile was observed in HIV-seropositive patients with delayed or absent disease progression, whereas progression of HIV infection was characterized by a weak type 1/strong type 2 cytokine production profile. PBMC of HIV-seropositive individuals are susceptible to antigen-induced cell death (AICD) after antigen recognition via T-cell receptor (TcR). While TcR-induced AICD is seen in CD4+ and CD8+ cells programmed cell death induced by recall antigens is preferentially observed in CD4+ cells, a situation more closely resembling the CD4 depletion of HIV infection. Because type 1 cytokines reduce, whereas type 2 cytokines augment T-lymphocyte AICD, an increase in the concentration of type 2 cytokines could result in the decline in CD4+ cells seen in HIV infection.
authors.forename: M
authors.initials: M
authors.lastname: Clerici
authors.forename: M L
authors.initials: ML
authors.lastname: Fusi
authors.forename: S
authors.initials: S
authors.lastname: Ruzzante
authors.forename: S
authors.initials: S
authors.lastname: Piconi
authors.forename: M
authors.initials: M
authors.lastname: Biasin
authors.forename: D
authors.initials: D
authors.lastname: Arienti
authors.forename: D
authors.initials: D
authors.lastname: Trabattoni
authors.forename: M L
authors.initials: ML
authors.lastname: Villa
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D018450:Disease Progression; D015658:HIV Infections / Q000503:physiopathology*; D006801:Humans; D007378:Interleukins / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
chemical_list: D016207:Cytokines; D007378:Interleukins