Influenza virus-specific human cytotoxic T cell clones: Heterogeneity in antigenic specificity and restriction by class II MHC products

Kaplan, David R.; Griffith, Rogers C.; Braciale, Vivian L.; Braciale, Thomas J.

doi:10.1016/0008-8749(84)90064-9

Cited by 91 publications

(36 citation statements)

References 22 publications

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“…In other systems, such as measles, herpes simplex, dengue and influenza virus responses, CD4* cytotoxic T cells have been reported [18][19][20][21]. However, these responses have been detected predominantly in prolonged ;•« (vVro cultures of PBL, or fallowing the stimulation of PBL wiih purified antigen or killed virus-In the present analysis, both CD4 ' and CD8 ^ CTLp were detected in the peripheral blood of adult donors following a single restimulation with infectious hPIV-l, Given these findings, it is of interest to note that several children with HIV infeetion and CD4' T cell lymphopenia have been reported to have persistent parainfluenza infection and prolonged viral excretion, in spile of the administration of preformed antibody [22].…”

Section: Discussionmentioning

confidence: 99%

Parainfluenza type 1 virus-infected cells are killed by both CD8+ and CD4+ cytotoxic T cell precursors

Slobod

Allan

1993

Clinical and Experimental Immunology

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SUMMARY The memory cytotoxic T lymphocyte (CTL) response to human parainfluenza type 1 virus (hPIV‐1), a prominent cause ol'respiratory infection in young children, has been analysed for a panel of healthy adults. The CTL response to the parainfluenza viruses has not been investigated previously. Precursor CTL (CTLp) with activity against hPI V‐1 ‐infected Epstein Barr virus (EBV)‐transformed B lymphoblastoid target cells were found at a relatively high precursor frequency (approximately 1/ 2500–1/4700 CD8+ and CD4+ subsets respectively) in peripheral blood. Both CD44 and CD8+ CTLp were delected by the analysis of individual microcultures set up under limiting dilution conditions from freshly isolated blood, the phenotype of the responder cell from individual wells being determined by flow cytometry. Further characterization of the CTL response demonstrated MHC restriction by the HLA‐A2 glycoprotein in 3/4 HLA‐A2′ donors. The presence of effective, hPIV‐1 ‐directed T cell memory may explain, in part, the protection observed in the adult population.

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Section: Discussionmentioning

confidence: 99%

Parainfluenza type 1 virus-infected cells are killed by both CD8+ and CD4+ cytotoxic T cell precursors

Slobod

Allan

1993

Clinical and Experimental Immunology

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“…Likewise, donor B effector cells lysed syngeneic but not allogeneic (donor A) targets. The small degree of cross-reactivity seen in the case of A effectors versus B targets may be due to unspecified but shared class I antigens or, possibly, the development of CD4+-mediated CTL activity, which has been described in cloned human populations (31,32). However, the latter is less likely given that no CD4+ CTLs are generated in our system (see below).…”

Section: Black Arrows) Pretreatment Of Dendritic Cells Withmentioning

confidence: 99%

“…If dendritic cells are key accessories in CTL induction, one would predict that these APCs should be effective in the generation of CTL responses to other antigens (e.g., melanoma antigens, alloantigens) where B7 is known to amplify the T cell response (43,45,46). The CD28-B7/BB 1 interaction provides a critical costimulatory mechanism for IL-2 gene expression (47)(48)(49) Influenza-specific CD4+ CTL have been described in both human and mouse systems (16,31,32). In contrast to CD8+ CTLs, CD4+ class H-restricted CTLs lysed target cells treated with noninfectious influenza virus or purified HA preparations and class II presentation was sensitive to lysosomotropic agents (16).…”

Section: Black Arrows) Pretreatment Of Dendritic Cells Withmentioning

confidence: 99%

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.

Bhardwaj¹,

Bender²,

González³

et al. 1994

J. Clin. Invest.

254

170

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Antigen-specific, CD8+, cytolytic T lymphocytes (CTLs) could potentially provide resistance to several infectious and malignant diseases. However, the cellular requirements for the generation of specific CTLs in human lymphocyte cultures are not well defined, and repetitive stimulation with antigen is often required. We find that strong CD8+ CTL responses to influenza virus can be generated from freshly isolated blood T cells, as long as dendritic cells are used as antigen presenting cells (APCs). Small numbers of dendritic cells (APC:T cell ratio of 1:50-1:100) induce these CTL responses from most donors in 7 d of culture, but monocytes are weak or inactive. Whereas both dendritic cells and monocytes are infected with influenza virus, the former serve as effective APCs for the induction of CD8+ T cells while the latter act as targets for the CTLs that are induced. The strong CD8+ response to influenza virus-infected dendritic cells is accompanied by extensive proliferation of the CD8+ T cells, but the response can develop in the apparent absence of CD4+ helpers or exogenous lymphokines. CD4+ influenza virus-specific CTLs can also be induced by dendritic cells, but the cultures initially must be depleted of CD8+ cells. These findings should make it possible to use dendritic cells to generate human, antigen-specific, CD8+ CTLs to other targets. The results illustrate the principle that efficient T cell-mediated responses develop in two stages: an afferent limb in which dendritic cells are specialized APCs and an efferent limb in which the primed T cells carry out an immune response to many types of presenting cells. (J. Clin. Invest. 1994. 94:797-807.)

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“…Potential antigenic sites that can be recognized by T lymphocytes are present in both regions when the hydrophobicity and predicted secondary structure of the protein are considered (6). Antiviral T lymphocytes are able to recognize either conserved or variable antigenic sites on viruses such as influenza (7) and herpes simplex virus (8), but similar patterns of reactivity by human T cells against HIV have not yet been demonstrated. We report here the generation of clonal HIVspecific T helper cell lines, derived from PBMC of a healthy HIV seropositive individual.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, only supernatants from those cultures in which proliferation was detected contained IL 2 (Table III). Many IL 2-producing human CD4+ T cell lines have the ability to mediate class II HLA-restricted virus-specific cytotoxic activity (7,8). More recently, cloned CD4+ cells established from the peripheral blood of chimpanzees infected with recombinant vaccinia viruses that express HIV envelope glycoproteins have been shown to mediate HIV-specific cytotoxic activity (20).…”

Section: Introductionmentioning

confidence: 99%

Identification of human immunodeficiency virus (HIV) envelope type-specific T helper cells in an HIV-infected individual.

Walker

Steimer²,

Rosenthal³

et al. 1988

J. Clin. Invest.

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MethodsTwo T helper cell clones recognizing the gp 120 envelope protein of HIV were generated from the peripheral blood of a healthy seropositive individual. These cells were type specific as they proliferated and produced IL 2 when stimulated by an epitope in the amino-terminal half of gp 120 of HIVsF2, but not by a similar region of HIVz,6, a Zairian HIV-1 isolate. These two viruses differ by 26% in the deduced amino sequence of the gp 120 protein. Moreover, the antigenic site(s) recognized by the cloned T cells are distinct from those recognized by envelope-specific antibodies. These observations have important implications for the development and use of anti-HIV vaccines.

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Influenza virus-specific human cytotoxic T cell clones: Heterogeneity in antigenic specificity and restriction by class II MHC products

Cited by 91 publications

References 22 publications

Parainfluenza type 1 virus-infected cells are killed by both CD8+ and CD4+ cytotoxic T cell precursors

Parainfluenza type 1 virus-infected cells are killed by both CD8+ and CD4+ cytotoxic T cell precursors

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.

Identification of human immunodeficiency virus (HIV) envelope type-specific T helper cells in an HIV-infected individual.

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