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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence is accumulating to suggest the existence of polarized human T-cell responses, reminiscent of TH1 and TH2 subsets described for mouse T cells. Human TH1 cells preferentially develop during infections by intracellular bacteria and trigger phagocyte-mediated host defense, whereas TH2 cells, which predominate during helminthic infestations and in response to common environmental allergens, are responsible for phagocyte-independent host response. Human TH1 and TH2 cells exhibit not only different functional properties but probably also distinct surface markers; TH2, but not TH1, clones express membrane CD30 and release the soluble form of CD30, a member of the TNF receptor superfamily. The cytokine profile of "natural immunity" evoked by different offending agents in the context of different host genetic backgrounds appears to be the most critical factor in determining the phenotype of the subsequent specific response. IL-12 and IFN-alpha and gamma produced by macrophages and NK cells favor the development of TH1 cells, whereas the early production of IL-4 by a still-unidentified cell type favors the development of TH2 cells. Clearly, polarized human TH1 and TH2 responses not only play different roles in protection, they can also promote different immunopathological reactions. Strong and persistent TH1 responses seen to be involved in organ-specific autoimmunity, contact dermatitis, and some chronic inflammatory disorders of unknown etiology. In contrast, polarized TH2 responses favor a reduced protection against the majority of infectious agents (including HIV) and, in genetically predisposed hosts, are responsible for triggering of allergic atopic disorders.
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PMID:Biology of human TH1 and TH2 cells. 755 14

Patterns of cytokine expression were analyzed in polyclonal and antigenic responses in children with perinatal HIV infection. Responses of PBL to PMA and A23187 calcium ionophore studied in patients in different stages of HIV infection revealed reduced levels of IL-2 in HIV-infected children beginning before 6 mo of age, and age-dependent increases in expression of IL-4, IL-10, and IFN-gamma. The levels of IL-4, IL-10, and IFN-gamma expression did not differ significantly between HIV-infected and age-matched uninfected children of HIV-seropositive mothers, except for a small reduction in HIV-infected children in late stages of infection. Responses to PHA, HLA alloantigens, HIV envelope peptides T1 and P18, and tetanus toxoid were studied in PBMC derived from asymptomatic and mildly symptomatic HIV-infected children. IL-2, IFN-gamma, IL-4, and IL-5 expression was detected in PHA-stimulated PBMC from all analyzed patients. HIV-infected children who failed to respond to HLA alloantigens, tetanus toxoid, or the envelope peptides had lower numbers of CD4+ cells and expressed, on PHA stimulation, higher levels of IL-4 and IL-5 and lower levels of IL-2 and IFN-gamma than patients who responded to the antigenic stimulation. Results of these analyses suggest that cytokine expression in HIV-infected children depends on the character of the stimuli as well as the phenotype of PBMC, and indicate possible prevalence of Th2 Ag-specific responses during the progression of HIV-induced immunodeficiency.
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PMID:Cytokine patterns during progression to AIDS in children with perinatal HIV infection. 756 Nov 17

Lymphocytes from patients with HIV-infection have been shown to undergo accelerated spontaneous apoptosis. Binding of CD4 molecules by HIV envelope protein gp120 and anti-gp120 antibodies can lead to crosslinking of CD4 molecules (CD4XL) in vitro and conceivably in vivo. We have recently shown that CD4XL in vitro, when performed in unfractioned peripheral blood mononuclear cells (PBMC) on normal HIV seronegative donors, is by itself sufficient to induce T cell apoptosis (Blood 82:3392, 1993). To further examine the mechanisms involved in apoptosis, we have examined the expression of Fas antigen (Fas) using 3 color flow cytometry. Fas is a cell surface molecule known to mediate apoptosis-triggering signals. We induced CD4XL in PBMC obtained from normal donors, either by anti-CD4 mAb Leu3a or by HIV-1 envelope protein gp160. PBMC subpopulations were examined for Fas Ag expression and for apoptosis induction by flow cytometry. CD4XL was found to result in increased Fas expression as well as Fas mRNA in lymphocytes and the up-regulated Fas Ag was closely correlated with apoptotic cell death. CD4XL in PBMC also resulted in induction of the cytokines INF-tau and TNF-alpha in the absence of IL-2 and IL-4 secretion. Both these cytokins contributed to Fas Ag up-regulation and antibodies to TNF-alpha and INF-tau abrogated CD4XL-induced Fas up-regulation and T-cell apoptosis. These findings suggest that CD4XL occurring in vivo might play an important role in inducing an abberant cytokine profile (which has been observed in HIV infected individuals) and also in triggering of T-cell apoptosis.
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PMID:Mechanism of apoptosis in peripheral blood mononuclear cells of HIV-infected patients. 757 84

Interleukins produced by both lymphoid and non-lymphoid cells play a crucial role in the immune response. This paper discusses the possible interleukin network in the immunopathogenesis of some oral diseases. In chronic inflammatory periodontal diseases and periapical inflammation, interleukins such as IL-1 and IL-6 may be responsible in tissue destruction. High levels of IL-12 but not IL-4 and IL-10 may reduce the course of candidal infection. The progression of HIV infection has been associated with the regulation of distinct cytokines; thus, the pathogenesis of Kaposi's sarcoma may be regulated by IL-6. In autoimmune-associated oral diseases such as lichen planus, the role of Langerhans cells in presenting autoantigens may parallel with increased levels of IL-6. It seems, therefore, that the course of these diseases is regulated by these polypeptides which may in turn modulate the disease severity. However, whether altered levels of interleukins in certain oral disorders can be used as a diagnostic marker requires further investigation.
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PMID:The interleukin network in the immunopathogenesis of oral diseases. 761 13

Individuals infected with Toxoplasma gondii normally develop resistance to the parasite, resulting in an asymptomatic chronic infection. In AIDS patients, this resistance is lost leading to reactivation of infection and development of encephalitis. To characterize the cytokine response of T. gondii-infected individuals, PBMC were cultured in vitro in the presence or absence of crude tachyzoite Ags (STAg). When stimulated with STAg, PBMC from T. gondii-infected donors, but not controls, produced high levels of Type 1 lymphokines (IL-2 and IFN-gamma) as well as the monokine IL-12, in the absence of detectable Type 2 lymphokines (IL-4 and IL-5). In contrast, cells of individuals from both groups produced high levels of IL-1, IL-6, and TNF-alpha when exposed to the same Ag preparation. By using highly purified elutriated cells, we demonstrated that monocytes are a major source of these monokines. The above findings were further expanded by analyzing the cytokine responses induced by STAg in PBMC from patients co-infected with T. gondii and HIV. Our results demonstrate that parasite-specific IL-2 and IFN-gamma responses are greatly impaired even before AIDS development, as is IL-12 synthesis by PBMC from HIV-infected individuals stimulated with STAg. In contrast, the release of IL-6 and TNF-alpha triggered by STAg is either not affected or augmented during HIV infection.
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PMID:HIV infection suppresses type 1 lymphokine and IL-12 responses to Toxoplasma gondii but fails to inhibit the synthesis of other parasite-induced monokines. 763 18

Kaposi's sarcoma (KS) is both an AIDS-defining disease and the most common HIV-associated malignancy. A cytokine-mediated pathogenesis for AIDS-KS is implicated because AIDS-KS-derived cell strains both respond to and express a variety of cytokines. We have reported the establishment of several (n = 18) AIDS-KS cell strains and determined that reduced exogenous growth factors are necessary to sustain proliferation in isolates from high histologic grade KS lesions. This current investigation explored the possibility that there are histologic grade-associated differences in either the qualitative and/or quantitative constitutive release of AIDS-KS growth stimulatory cytokines. Our findings showed that the incorporation of HTLV-II cytokine-rich conditioned media induced both qualitative and significant quantitative cytokine release, suggesting that exogenous growth promoters stimulate constitutive cytokine release. ELISA of our AIDS-KS cell strains demonstrated constitutive release of IL-6 (seven of seven), FGF-2 (five of seven), GM-CSF (three of seven), and IL-1 beta (one of seven). None of our AIDS-KS cell strains constitutively released detectable levels of Onco-M, IL-4, PDGF, TNF-alpha, or TNF-beta. In addition, we report that the method of cytokine result quantitation significantly affects reported cytokine levels. We determined that there was no significant histologic grade-dependent difference in the constitutive release of soluble cytokines by in vitro grown cultures of AIDS-KS cells. The presence of HIV influenced the sera cytokine profiles by elevating IL-6 and decreasing PDGF concentrations of HIV+ individuals relative to HIV- healthy controls. However, the presence of KS was not associated with unique serum cytokine profiles, because no differences were noted in comparisons of HIV+/KS+ versus HIV+/KS- individuals. Our findings suggest that the local environment is key in modulating AIDS-KS cytokine expression and that KS growth-promoting factors function at the local or paracrine, not the systemic, level. In conclusion, our previous results demonstrated a histologic grade-associated difference in the in vitro growth capacity of AIDS-KS cells; with high histologic grade isolates displaying a marked growth advantage during culture in minimally supplemented media. Findings from this current study reveal that although the potential for a constitutive growth loop exists in the high-grade isolates, it is not reflected in the free levels of soluble cytokines secreted into the culture medium.
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PMID:Comparison of constitutive cytokine release in high and low histologic grade AIDS-related Kaposi's sarcoma cell strains and in sera from HIV+/KS+ and HIV+/KS- patients. 764 50

Cytokine responses are dramatically affected when HIV-1 infected cells are activated with certain antigenic stimuli. We report the effects of HIV-1 tat gene in cytokine modulation, using HIV-1 tat transfected T (Jurkat) and B (Raji) cell lines. Studying the effect of tat and/or PMA + PHA on mRNA expression of 14 cytokines (IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha, TNF-beta, GM-CSF, TGF-beta, IFN-gamma and MIP-1 alpha) illustrated differential effects. In addition to the varied effects of tat on the steady state levels of cytokine mRNAs, tat induced the secretion of TNF-beta preferentially in both B and T cell lines, either by itself as in Raji B cell line or synergistically upon PMA + PHA stimulation as in Jurkat T cell line.
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PMID:Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines. 769 26

Previous studies demonstrated that mucosal HIV p24 antigen content varied during the progression of HIV infection. In this study, expression of HIV RNA and mRNA of selected cytokines was examined in rectal mucosa from HIV-infected individuals. Rectal biopsies from 27 subjects were studied: 7 with CD4 counts > 500/mm3 (early), 11 with CD4 < 500 (intermediate), and 9 with AIDS (late), plus 4 HIV-seronegative controls. RNA in situ hybridization was performed using 35S-labeled riboprobes of HIV, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, INF-alpha, IFN-gamma, and TGF-beta. HIV RNA was detected more frequently in the intermediate group than in the other groups (p < 0.005). Cytokine mRNA expression also varied during disease progression. The expression of IFN-alpha, IFN-gamma, and TGF-beta mRNA was most prevalent early in the disease; peak expression of IL-4, IL-5, IL-6, and IL-10 was seen during the intermediate stage, and peak expression of TNF-alpha and IL-1 beta mRNA were seen in AIDS patients. HIV RNA and cytokine mRNA expression vary during HIV disease progression. HIV RNA expression is greatest in the intermediate stage of the disease. The pattern of cytokine mRNA expression suggests predominant cell-mediated immunity under basal conditions and early in the disease, generalized cytokine activation in its middle phase, and proinflammatory cytokine activation in AIDS patients. Cytokine modulation of HIV expression in rectal mucosa in vivo may occur and have pathogenic importance.
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PMID:Variation in the expression of human immunodeficiency virus RNA and cytokine mRNA in rectal mucosa during the progression of infection. 770 12

In vitro experiments using purified rat CD4+ T cells in primary and secondary mixed leukocyte cultures (MLC) have been carried out to explore the mechanism of inhibition of cell-mediated autoimmune disease in the rat by a nondepleting monoclonal antibody (mAb) to CD4. Previous work has shown that W3/25, a mouse anti-rat CD4 mAb of immunoglobulin G1 isotype, completely prevents the development of the paralysis associated with experimental allergic encephalomyelitis (EAE) in Lewis rats, but does so without eliminating the encephalitogenic T cells. The in vitro experiments described in this study have shown that when CD4+ T cells were activated in the presence of the anti-CD4 mAb in a primary MLC, the synthesis of interferon (IFN) gamma, but not interleukin (IL) 2, was completely inhibited. After secondary stimulation, now in the absence of the mAb, the synthesis of IL-4 and IL-13 mRNA was greatly enhanced compared with that observed from CD4+ T cells derived from primary cultures in which the mAb was omitted. As IL-4 and IL-13 are known to antagonize cell-mediated immune reactions, and as EAE is cell-mediated disease, the data suggest that the W3/25 mAb controls EAE by modifying the cytokine repertoire of T cells that respond to the encephalitogen. The capacity for the mAb to suppress IFN-gamma synthesis provides, in part, an explanation for this change in cytokine production. These findings are discussed in terms of what is known of the factors that determine which cytokine genes are expressed on T cell activation. Possible implications for the evolution of T cell responses in human immunodeficiency virus infection are also discussed.
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PMID:Activation of CD4+ T cells in the presence of a nondepleting monoclonal antibody to CD4 induces a Th2-type response in vitro. 779 Aug 23

T-cell adjuvancy involves the use of agents to stimulate preferentially delayed type hypersensitivity (DTH). Traditional adjuvants like Alum, Freunds, muramyl peptides, and endotoxins are not selective. Natural infection (e.g. vaccinia) may yield selective DTH. Low dose cyclophosphamide (CY) with mycobacteria was the first experimental T-cell adjuvant. New adjuvant formulations (ISCOMS, MAPS, etc.) with synthetic T-cell epitopes offer improved formulations. Upregulation of TH-1 helper cells and their actions with interleukins like IL-2, IL-12, and gamma IFN or antibodies to IL-4 and IL-10 may augment potently pathogen and tumor resistance. Similarly, transfection of tumor target cells with genes for IL-2, IL-12, gamma IFN, etc., offers novel vaccine treatment approaches. Finally, "thymomimetic" peptides like thymosin alpha 1 or drugs like levamisole or isoprinosine alone or in conjunction with interleukins may augment TH-1 and DTH responses. These approaches are seeing increasing emphasis in new treatment strategies for cancer and infections like HIV.
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PMID:T-cell adjuvants. 780 29


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