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Dive into the research topics where G. Li Pira is active.

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Featured researches published by G. Li Pira.


Human Immunology | 1998

Repertoire breadth of human CD4+ T cells specific for HIV gp120 and p66 (primary antigens) or for PPD and tetanus toxoid (secondary antigens)

G. Li Pira; L. Oppezzi; M. Seri; M Westby; F. Caroli; Daniela Fenoglio; F. Lancia; Anna Maria Ferraris; Laura Bottone; M. T. Valle; Annalisa Kunkl; G. Romeo; Angus G. Dalgleish; Fabrizio Manca

Antigen derived peptides bound on MHC class II molecules on presenting cells stimulate specific CD4 lymphocytes that are in a naive state if antigen is given for the first time, or in a memory state if antigen has been previously encountered. In order to compare clonal heterogeneity of the human CD4+ T helper repertoire in primary vs. recall responses, we have generated T cell lines in vitro by repeated stimulation of peripheral lymphocytes with primary or with recall antigens. Clonal heterogeneity was broad in the case of recall response to tetanus toxoid or PPD, with a high frequency of specific precursors (> 100 cells/10(6) lymphocytes). In contrast, T cell lines responsive to primary antigens (HIV gp120 or HIV p66) were oligoclonal as defined by TCR V beta gene usage and by spectratyping, and the precursor frequency was low (< 2 cells/10(6) lymphocytes). Primary T cell lines generated from blood samples drawn at different times from the same donor showed that clones with identical TCR CDR3 region coding sequences were expanded, suggesting that in these individuals a large progeny derived from one single precursor is present, even though a previous encounter with the antigen was not documented. Assuming an even in vivo distribution of such cells, the presence of one precursor every 10(6) CD4 lymphocytes (within the CD4 T repertoire that comprises roughly 10(11) CD4 T cells) indicates that approximately 10(5) identical T cells from the same clonal precursor account for the primary response against the model antigens we have studied.


Gene Therapy | 1997

Anti-HIV genetic treatment of antigen-specific human CD4 lymphocytes for adoptive immunotherapy of opportunistic infections in AIDS

Fabrizio Manca; Daniela Fenoglio; Elisa Franchin; Daniele Saverino; G. Li Pira; F. Buffa; D Bignardi; L Del Pup; Giorgio Palù

HIV-1 infection results in the loss of CD4+ T helper lymphocytes which make up the immune repertoire. This leads to opportunistic infections that define AIDS. Here, we show that CD4 T cell lines from normal donors with specificity for different antigens can be rendered resistant to HIV-1 replication by retroviral transduction with an antisense vector directed to the HIV-1 tat gene. The genetic treatment did not affect the properties of antigen-specific CD4 lymphocytes such as proliferative response, lymphokine production and phenotypic markers. The HIV-1 challenge dose that resulted in productive infection was two to four logs higher for transduced cells as compared with control cells. Resistance was shown with the HXB2 strain, whose tat sequence was used to design the antisense gene, and with the SF2 strain, whose targeted tat sequence carries five nucleotide mismatches. Retroviral transduction was also performed on a Candida-specific T cell line from a seropositive individual. This line, derived from T cells infected in vivo, produced infectious virus when stimulated in vitro with antigen, but was no longer productive after transduction. In addition, a four log higher HIV-1 challenge dose was needed for a productive superinfection of this T cell line. The production of antigen-specific CD4 T cells resistant to HIV-1 replication to be used in adoptive immunotherapy of opportunistic infections may represent a new form of gene therapy of AIDS.


Journal of Acquired Immune Deficiency Syndromes | 1995

Human CD4+ T cells can discriminate the molecular and structural context of T epitopes of HIV gp120 and HIV p66

F. Manca; Daniela Fenoglio; M. T. Valle; G. Li Pira; Annalisa Kunkl; Anna Maria Ferraris; Daniele Saverino; F. Lancia; Lorenzo Mortara; Luisa Lozzi; M. Pierres; Angus G. Dalgleish; G. Lewis

CD4+ T cell lines and clones specific for human immunodeficiency virus (HIV) antigens have been generated from peripheral lymphocytes of naive individuals by priming with the envelope protein gp120, the enzyme reverse transcriptase (p66), and their synthetic peptides. T cells were tested for proliferation to proteins, to peptides, and to HIV virions. Different patterns of reaction were identified. T cells primed in vitro with the whole antigen responded to the protein, but recognition of overlapping peptides occurred with a fraction of the lines or clones. The virus was recognized by some, but not all, of the gp120- and p66-specific T cells, with an efficiency 2 logs higher than the recombinant soluble proteins on a molar basis. One T cell line specific for gp120 responded to virions presented by B cells, but not by monocytes. In contrast, T cells induced with peptides did not always respond to the proteins. Generation of T cell lines from naive individuals may be an in vitro model for T cell immunization, and the response patterns may have implications for the design of vaccines aimed at inducing a T helper response. In fact our in vitro data suggest that (a) immunization with peptides does not always induce T cells recognizing the whole protein, (b) immunization with proteins does not always induce T cells recognizing the protein in the context of the HIV virus, and (c) recognition of gp120 in the context of HIV may be dictated by the type of presenting cells.


Clinical and Experimental Immunology | 2002

Preservation of clonal heterogeneity of the Pneumocystis carinii-specific CD4 T cell repertoire in HIV infected, asymptomatic individuals

G. Li Pira; Daniela Fenoglio; L. Bottone; Paola Terranova; Emanuele Pontali; F. Caroli; M. Seri; J.-C. Cailliez; Gerrit Koopman; Roberto S. Accolla; F. Del Galdo; G. Abbate; R. De Palma; F. Manca

The loss of CD4 lymphocytes in HIV disease associates with opportunistic infections. Since diverse CD4 T cell clones respond to an opportunistic pathogen, we asked whether CD4 depletion deletes selected clones in the repertoire (vertical depletion) or it affects all clones by reducing the cell number in each progeny without affecting the overall number of clones (horizontal depletion). Understanding this point may help explain the mode of CD4 depletion and the mode of immunoreconstitution after therapy. Therefore we examined the CD4 T cell repertoire specific for Pneumocystis carinii, a relevant opportunistic pathogen in AIDS, in HIV‐infected, asymptomatic individuals. We identified two patients of 36 asymptomatics for lack of proliferation to P. carinii, suggesting selective depletion of specific CD4 cells. To investigate clonal heterogeneity of P. carinii‐responsive CD4 lymphocytes, specific CD4 T cell lines were generated and studied by TCR BV gene family usage and CDR3 length analysis (spectratyping). Clonal heterogeneity was similar in antigen‐specific CD4 lines generated from P. carinii non‐responding HIV seropositives and from controls. Thus, despite undetectable response to the pathogen, residual specific cells probably prevent overt infection and, when expanded in vitro, exhibit a clonal diversity similar to normal controls. These findings suggest a horizontal, rather than vertical, depletion in these asymptomatic patients.


Gene Therapy | 2001

Genetically modified immunocompetent cells in HIV infection

Giorgio Palù; G. Li Pira; Francesca Gennari; Daniela Fenoglio; C. Parolin; F. Manca

Even in the era of highly active antiretroviral therapy (HAART), gene therapy (GT) can remain a promising approach for suppressing HIV infection, especially if complemented with other forms of pharmacological and immunological intervention. A large number of vectors and targets have been studied. Here we discuss the potential of genetically treated, antigen-specific immunocompetent cells for adoptive autologous immunotherapy of HIV infection. Cellular therapies with gene-modified CD8 and CD4 lymphocytes are aimed at reconstituting the antigen-specific repertoires that may be deranged as a consequence of HIV infection. Even if complete eradication of HIV from the reservoirs cannot be achieved, reconstitution of cellular immunity specific for opportunistic pathogens and for HIV itself is a desirable option to control progression of HIV infection and AIDS pathogenesis better.


Research in Virology | 1996

Handling of retroviral antigens by human antigen-presenting cells

Daniela Fenoglio; G. Li Pira; Daniele Saverino; Anna Maria Ferraris; F. Lancia; Annamaria Megiovanni; L. Oppezzi; Gabriella Piatti; F. Buffa; M. T. Valle; Annalisa Kunkl; Fabrizio Manca

Antigen-specific T helper cells play an important role in retroviral infections. Indeed, they provide help for B-cell activation and antibody production and for clonal expansion of cytolytic lymphocytes. Therefore, we used retrovirus-specific human T helper clones in order to define modes of antigen presentation, antigen-presenting cells and the molecular context of Th epitopes that could be exploited in the design of immunogens aimed at optimizing the Th cell response. In particular, we describe several mechanisms of receptor-mediated antigen uptake that enhance the stimulation of human T-cell clones specific for HIV and HTLV-1 antigens; we report on the differential recognition of Th epitopes depending on the molecular-viral context; we show that dendritic cells are the most efficient presenting cells and are essential for the induction of in vitro primary Th cell responses; and finally, we propose that Th cells specific for internal, conserved antigens of HIV such as reverse transcriptase, may be candidates for intrastructural help resulting in induction of envelope specific antibodies.


Journal of Acquired Immune Deficiency Syndromes | 1994

Dendritic Cells Are Potent Antigen-presenting Cells for In Vitro Induction of Primary Human Cd4 T-cell Lines Specific for Hiv gp120

F. Manca; G. Li Pira; Daniela Fenoglio; Sun Pei Fang; A. Habeshaw; S. C. Knight; Angus G. Dalgleish


Minerva Biotecnologica | 2002

CD4 and CD8 epitope mapping of cytomegalovirus tegument protein pp65 for diagnostic, vaccinal and therapeutic purposes.

G. Li Pira; L. Bottone; Federico Ivaldi; Roberta Pelizzoli; Lorenzo Mortara; Arianna Loregian; Laura Bracci; Luisa Lozzi; Giorgio Palù; F. Manca


Minerva Biotecnologica | 2001

Human CD4 T-cell repertoires specific for opportunistic pathogens.

G. Li Pira; L. Bottone; Paola Terranova; I Mortara; Federico Ivaldi; Francesco Del Galdo; Daniela Fenoglio; Annalisa Kunkl; Arianna Loregian; Giorgio Palù; R. De Palma; F. Manca


Human Immunology | 1998

Erratum: Repertoire breadth of human CD4+ T cells specific for HIV gp120 and p66 (primary antigens) or for PPD and tetanus toxoid (secondary antigens) (Human Immunology (1998) 59 (137))

G. Li Pira; L. Oppezzi; M. Seri; Mike Westby; F. Caroli; Daniela Fenoglio; F. Lancia; Anna Maria Ferraris; L. Bottone; M. T. Valle; Annalisa Kunkl; G. Romeo; Angus G. Dalgleish; F. Manca

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F. Manca

Istituto Giannina Gaslini

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L. Bottone

University of Insubria

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