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I Moreno de Alborán

Publications and source records attributed to I Moreno de Alborán.

5 recordsLinked to original sources
PubMed2004

c-Myc-deficient B lymphocytes are resistant to spontaneous and induced cell death.

C-myc gene is a member of the myc family of proto-oncogenes involved in proliferation, differentiation, and apoptosis. Overexpression of c-myc in fibroblasts causes apoptosis under low serum conditions in a process that requires the interaction of CD95 and CD95L on the surface. We have previously reported an in vivo conditional model to inactivate the c-myc gene in B lymphocytes. Here, we show that c-Myc-deficient primary B lymphocytes are resistant to different apoptotic stimuli. Nonactivated c-Myc-deficient B cells are resistant to spontaneous cell death. Upon activation, c-Myc-deficient B lymphocytes express normal surface levels of activation markers, and show resistance to staurosporine and CD95-induced cell death.

Animals↗
PubMed1995

Human monoclonal Fab fragments specific for viral antigens from combinatorial IgA libraries.

BACKGROUND: IgA constitutes the first line of immune defense, interacting with a variety of environmental antigens. Following infection with respiratory syncytial virus (RSV) individuals frequently exhibit elevated serum IgA titers specific for the virus. Previously combinatorial IgG libraries have successfully been used to clone such human antibody responses. OBJECTIVES: Here we evaluate the possibility of constructing combinatorial IgA libraries on the surface of filamentous phage to retrieve human viral-specific IgA Fab fragments. STUDY DESIGN: Bone marrow from an HIV-1 seropositive donor was used as RNA source to construct combinatorial IgA kappa and lambda libraries of approximately 10(7) clones. RESULTS: By affinity selection using an immobilized recombinant RSV FG protein, two unique IgA Fab fragments producing clones (AD5 and AD23) reactive with the selecting antigen were isolated. One of the Fab fragments was found to be specific for RSV F glycoprotein and bind with high apparent affinity (2 x 10(8) M-1). The other binds with lower affinity and exhibits cross-reactivity with other antigens. CONCLUSION: The strategy described, involving construction of combinatorial IgA libraries on the surface of filamentous phage, should be generally applicable to the investigation of both mucosal and systemic human IgA immune responses, and may become an important tool for evaluation of mucosal vaccine regimes.

Amino Acid Sequence↗
PubMed1993

Immunoregulation by cytokines.

The study of cytokine biology relevant to the in vivo (patho)physiology of the immune response is complicated by a series of features inherent to the cytokine system. The present survey focuses on the mechanisms governing the function of cytokines that may give rise to methodological and conceptual problems concerning in vivo manipulations of immunologically relevant cytokines. Special emphasis is laid on the complex interrelation between individual cytokines (cascades, synergy, anergy, pleiotropism, and redundancy), as well as on the mechanisms that guarantee a compartmentalization of cytokines, i.e., a chronological, spatial, cell-type differentiation stage, and activation-dependent restriction of their function. The in vivo effects of cytokines can be studied either by augmenting their concentration or reducing their bioavailability. The advantages of local and systemic cytokine injections, usage of transgenes, or expression as gene products encoded by recombinant viruses are discussed and contrasted with different manipulations provoking cytokine deficiencies, namely the application of cytokine antagonists, neutralizing antibodies and receptor derivates, receptor-targeted cytotoxic drugs, and germ line disruption of cytokine genes. Both types of intervention are afflicted with major problems. Whereas providing an excess of cytokines in vivo, especially at the systemic level, constitutes an essentially non-physiological intervention, the induction of cytokine deficiencies will only unravel essential effects, but is incapable of elucidating the many pleiotropic cytokine effects that, by virtue of the redundancy of the system, compensate for each other.

Animals↗
PubMed1992

Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is independent of the interleukin-2 pathway.

Injection of the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) into mice provokes a rapid expansion and subsequent contraction of the pool of SEB-reactive T cells bearing T cell receptor (TcR) V beta 8 gene products. Given that interleukin 2 (IL-2) stimulates proliferation, abolishes anergy, and counteracts apoptotic cell death in T cells in vitro, we tested whether the IL-2 synthesis inhibitor cyclosporin A (CsA) or a vaccinia virus recombinant releasing high amounts of human IL-2 modulate SEB responses in vivo. Surprisingly, neither IL-2 nor CsA were able to change the in vivo kinetics and magnitude of SEB-induced expansion, unresponsiveness to SEB, and peripheral clonal deletion of T cells expressing products of the SEB-reactive TcR V beta 8 gene family. In accord with these in vivo observations, IL-2 is incapable of reversing "anergy" and apoptotic cell death of V beta 8+ SEB-reactive T cells isolated from SEB-primed mice in vitro. Accordingly, upon SEB injection V beta 8+ T cells expand rapidly, without expressing IL-2 receptor (IL-2R)alpha chains in vivo, although SEB induces IL-2R alpha in vitro. Altogether, these results indicate that the IL-2/IL-2R-mediated pathway is not involved in T cell repertoire modulation by bacterial superantigens. Moreover, the data suggest that unresponsiveness of V beta 8+ T cells from SEB-primed mice is not a reversible process, but involves an unreversible commitment to programmed cell death. Absence or presence of IL-2 responsiveness could be a hallmark to distinguish truly reversible anergy and peripheral clonal deletion.

Animals↗