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Biomedical subjects

I Bourgault

Publications and source records attributed to I Bourgault.

15 recordsLinked to original sources
PubMed1992

Cytotoxic T lymphocyte response against multiple simian immunodeficiency virusA (SIV) proteins in SIV-infected macaques.

To identify the target proteins of CD8+ T lymphocytes we have explored the cytolytic immune responses of 12 rhesus macaques experimentally infected with the simian immunodeficiency virus (SIVmac). Target cells were autologous B cell lines presenting SIVmac proteins after infection with recombinant vaccinia viruses. The eight following proteins were studied: ENV, POL, GAG, NEF, VIF, REV, TAT, and VPX. Macaque PBMC stimulated with Con A and expanded in T cell growth factor-containing medium produced cell lines with cytolytic activity in the majority of infected animals (9/12). The structural proteins ENV, POL, and GAG were recognized by cell lines derived from nine, eight, and six macaques, respectively. The small regulatory proteins also represented efficient CTL targets, a specific activity being detected against NEF (8/12), REV (7/12), VPX (7/12), TAT (6/12), and VIF (5/12). Most cytotoxic responses (except those directed against ENV) were mediated by CD8 cells and were MHC class I restricted. Limiting dilution analysis allowed us to quantify the frequency of CTL precursors and confirmed the high immunogenicity of multiple SIV proteins. Three different patterns of response could be defined: six animals were able to recognize at least six of the eight tested target proteins, two of them reacting with all eight target proteins. The other three responder macaques reacted only against a few SIV proteins, whereas no cytotoxic activity was detected in the three remaining infected macaques and in the nine negative controls. The six animals responding against multiple proteins were still healthy 12 to 22 mo after infection with two of them presenting a decrease in circulating CD4 cells concurrently to the disappearance of the CTL response. Conversely, three nonresponder or low responder macaques developed an overt disease after 4 to 12 mo, and two other presented a very low level of CD4 cells, suggesting that the pattern of response may be of prognostic value.

Animals↗
PubMed1992

Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases.

BACKGROUND: Toxic epidermal necrolysis is a potentially severe mucocutaneous affliction whose cause is usually drug related. To further characterize the nature of the dermal mononuclear infiltrate as well as the epidermal alterations observed by standard microscopy, we studied five cases of toxic epidermal necrolysis using labeled monoclonal antibodies. RESULTS: On clinically involved areas of skin, the following occurs: (1) the dermal infiltrate is composed mainly of activated T lymphocytes, with a predominant helper phenotype; (2) the number of Langerhans cells is decreased; and (3) keratinocytes express HLA-DR molecules, normally absent on their surface. CONCLUSIONS: These findings, although not specific, are consistent with an immune cellular reaction, but they could also be linked to an inflammatory reaction initiated by epidermal damages whatever its primary mechanism.

Adult↗
PubMed1992

Three epitopic peptides of the simian immunodeficiency virus Nef protein recognized by macaque cytolytic T lymphocytes.

In 8 of 12 experimentally infected macaques, the Nef SIVmac 251 protein was recognized by cytolytic T lymphocytes (CTL) and appeared strongly immunogenic. Here, we report experiments which have been performed by using synthetic peptides to precisely determine the epitopes recognized by macaque CTL. Three epitopes of the Nef protein have been defined as CTL targets in three macaques. The epitopic peptides are located in the central region of the protein, and all of them show high homology with peptides of the human immunodeficiency virus type 1 Nef protein recognized by human CTL in association with several human leukocyte antigen molecules. These results suggest that (i) the Nef protein is a good candidate for vaccination not only because of its early expression but also because of its high immunogenicity for CTL, (ii) long peptides covering the central region of this protein could be used as vaccines and could cross the major histocompatibility complex barrier in a large variety of individuals, and (iii) the rhesus macaque is a good animal model in which to test for protection by CTL.

Amino Acid Sequence↗
PubMed1991

Limiting-dilution analysis of the HLA restriction of anti-Epstein-Barr virus-specific cytolytic T lymphocytes.

Human Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes (CTL) play an important role in maintaining the virus/host equilibrium during persistent infections. We analysed precursors of anti-EBV CTL by the limiting-dilution technique. Seven healthy EBV-seropositive and two EBV-seronegative donors were tested. All the donors seropositive for EBV gave clear-cut positive results, and it was remarkable that the frequency of CTL precursors (CTLp) observed was much higher than that reported for other viruses. In contrast, in the seronegative donors the frequency of CTLp was undetectable. The CTLp were derived from the CD4-CD8+ population only, although EBV-specific CD4+ cytolytic T cell clones have been described. A study of the HLA restriction showed that some HLA-A or HLA-B antigens can function as preferential restricting molecules, but that CTLp restricted by the other HLA-A or HLA-B molecules also exist. However, the dominant population of CTL present in primary responses is sometimes different from that of long term cell lines established from the same donor.

B-Lymphocytes↗
PubMed1991

Transient intraepidermal bullous reaction after skin graft for toxic epidermal necrolysis. Ultrastructural and immunohistochemical features similar to those of inherited epidermolysis bullosa simplex.

Blister formation in skin graft donor or recipient sites is uncommon. We describe a 49-year-old female patient with bullae in sites of grafts used in the treatment of toxic epidermal necrolysis. Generalized loss of skin developed 3 weeks after she had ingested phenobarbital. Sixty days after the beginning of the toxic epidermal necrolysis, the reepidermization was only 80% and skin grafts were placed on lower-extremity and abdominal wounds using the first healed sites as donor sites. Several bullae and erosions were noted on grafted areas 3 weeks later. Skin biopsy specimens revealed separation at the dermoepidermal junction, and no autoantibodies were detected by direct and indirect immunofluorescence. Electron microscopy demonstrated that the blister was formed through the basal keratinocytes and that the dermoepidermal junction, including hemidesmosomes and anchoring fibrils, was normal. Immunofluorescence mapping was performed using polyclonal antibodies from the serum of patients with bullous pemphigold and epidermolysis bullosa acquisita and monoclonal antibodies against GB3 antigen and collagen type VII. All but the bullous pemphigold serum gave positive results; only faint and focal staining of the dermoepidermal junction was observed with bullous pemphigold serum. These findings are the same as those encountered in hereditary epidermolysis bullosa simplex. A biopsy performed 1 year later in the same site as the first one revealed that bullous pemphigold antigen was normally expressed. Keratinocytes autografted in the treatment of toxic epidermal necrolysis may become transiently, functionally abnormal because of the alteration of recipient sites.

Blister↗
PubMed1989

A virus-specific CD4+ cell-mediated cytolytic activity revealed by CD8+ cell elimination regularly develops in uncloned human antiviral cell lines.

Antiviral HLA class II-restricted cytotoxic CD4+ clones have been relatively well characterized in vitro but their significance in the immune response remains unknown. Here anti-influenza A and anti-EBV CD4+ CTL have been studied by using permanent cell lines either untreated or depleted of CD8+ cells. In bulk cultures, HLA class I-restricted anti-viral CD8+ CTL account for all of the detectable killer cell activity, whereas after elimination of CD8+ cells an HLA class II-restricted killer activity mediated by CD4+/2H4-/4B4+ cells was consistently observed. The CD4+ CTL were fully differentiated in all of the cultures tested from the third in vitro passage because they could be demonstrated immediately after elimination of CD8+ cells. These CD4+ killer cells were equivalent to the CD8+ cells in terms of their lytic capacity. The absence of any class II-restricted antiviral activity in bulk cultures seems to be related to the very small numbers of CD4+ cells present in these antiviral cell lines. However, CD4+ cytolytic activity could not be detected during the first two in vitro passages, even when limiting dilution analysis of the CTL precursors were performed, showing that the killer function of Th cells differentiate only after several in vitro stimulations.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Role of different lymphocyte subsets in human anti-viral T cell cultures.

We have systematically studied uncloned human cell lines derived from anti-influenza A virus or anti-Epstein-Barr virus (EBV) bulk cultures, or from cultures highly enriched for CD4+ or CD8+ lymphocytes. The most noteworthy results are the following: (1) Anti-viral bulk cultures consisted of more than 90% of CD8+ cells in all cases. In contrast, anti-HLA cell lines are composed of approximately 50% CD8+ and 50% CD4+ cells. All of the CD8+ and CD4+ cells present in the culture were also 4B4+/2H4-. (2) In anti-viral bulk cultures, the cytolytic activity was restricted by HLA class I molecules and almost exclusively through a single HLA class I molecule. (3) Positively or negatively selected CD8+ lines showed the same restriction pattern. They grew less efficiently than bulk cultures but could be maintained in the absence of CD4+ cells. The CD4+ cells were however necessary at the beginning of the culture for the development of cytolytic anti-influenza virus CD8+ cells, whereas they were not required for the development of cytolytic anti-EBV CD8+ cells. (4) The CD4+ cell lines grew more actively than bulk cultures. A cytolytic activity for virus-infected cells was constantly detected in these culture from the third passage onward and it was always restricted by HLA class II molecules. This activity was maintained throughout the culture period. However, class II-restricted cytolytic cells were not detected during primary or secondary responses in vitro.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Systemic polyarteritis nodosa diagnosed at hysterectomy.

A 61-year-woman was referred because of declining general health. A diagnosis of uterine malignancy was suspected on the basis of uterine enlargement and an elevated erythrocyte sedimentation rate. Hysterectomy was performed, and histologic examination revealed necrotizing vasculitis affecting the ovaries, fallopian tube, and uterus. Muscle biopsy showed typical periarteritis nodosa lesions. Despite the scarcity of such cases, the incidental finding of necrotizing arteritis in a surgical uterine specimen warrants further investigation to determine if the vasculitic process is localized.

Female↗