In Vitro Whole-Blood Analysis of Cellular Immunity in Patients with Active Coccidioidomycosis by Using the Antigen Preparation T27K

Ampel, Neil M.; Kramer, Larissa A; Li, Lijin; Carroll, Deborah S.; Kerekes, K. M.; Johnson, Suzanne M.; Pappagianis, Demosthenes

doi:10.1128/cdli.9.5.1039-1043.2002

Cited by 22 publications

(27 citation statements)

References 29 publications

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“…CD4 ϩ T cells (2.5 ϫ 10 6 ) and APCs (2.5 ϫ 10 6 ) were cocultured either in the presence of Coccidioides T27K antigen (40 g/ml medium) (46) or in medium alone and transferred to wells of a 24-well plate containing 1 ml of RPMI 1640 medium plus 10% (vol/vol) heat-inactivated FBS, 100 IU/ml penicillin, and 100 g/ml streptomycin. The T27K antigen is a multicomponent, soluble derivative of C. posadasii parasitic cell homogenates and has been shown to have protective activity against pulmonary coccidioidomycosis in mice (1). Supernatants of the stimulated immune T cells were collected after 48 h of incubation.…”

Section: Methodsmentioning

confidence: 99%

Vaccine Immunity to Coccidioidomycosis Occurs by Early Activation of Three Signal Pathways of T Helper Cell Response (Th1, Th2, and Th17)

et al. 2011

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Section: Methodsmentioning

confidence: 99%

Vaccine Immunity to Coccidioidomycosis Occurs by Early Activation of Three Signal Pathways of T Helper Cell Response (Th1, Th2, and Th17)

et al. 2011

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“…[ 3 H]thymidine incorporation was measured using a scintillation counter (TopCount; Perkin-Elmer). T27K has been previously demonstrated to specifically distinguish Coccidioides-immune donors from nonimmune donors (11,12,33). PBMC from all individuals tested were activated by phytohemagglutinin.…”

Section: Cytokines and Antibodiesmentioning

confidence: 99%

Spherules Derived from Coccidioides posadasii Promote Human Dendritic Cell Maturation and Activation

Dionne

Podany²,

Ruiz

et al. 2006

Infect Immun

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Previous studies have shown that dendritic cells (DC) pulsed with T27K, an antigenic preparation derived from spherules (of Coccidioides posadasii), activate peripheral blood mononuclear cells (PBMC) from nonimmune subjects as well as from patients with disseminated coccidioidomycosis. In this study, we have assessed the interaction between human DC and C. posadasii spherules in order to better understand the initial response between Coccidioides and the human host. Whole autoclaved spherules induced lymphocyte transformation in PBMC obtained from immune but not from nonimmune donors. Immature DC (iDC) bound fluorescein isothiocyanate-labeled spherules in a time-and temperature-dependent manner. This binding was blocked by the addition of mannan, suggesting mannose receptor involvement in the DC-Coccidioides interaction. Binding was subsequently associated with ingestion and intracellular processing of spherules. Coculturing of spherules with iDC was associated with the development of mature DC that were morphologically, phenotypically, and functionally similar to those induced by tumor necrosis factor alpha and prostaglandin E 2 . Finally, spherules incubated with iDC induced activation of PBMC from nonimmune donors. These data indicate that human DC are capable of binding, internalizing, and presenting antigens from Coccidioides spherules and suggest that DC may play a critical early role in the formation of a cellular immune response in human coccidioidomycosis.

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“…More recently, in vitro studies have shown that peripheral blood T lymphocytes from individuals with well-controlled infection produce gamma interferon (IFN-␥) in response to coccidioidal antigen, while cells from individuals with disseminated disease do not (1). Failure of T lymphocytes to react to coccidioidal antigen in vitro is associated with a poorer clinical score among those with disseminated disease (2).…”

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confidence: 99%

Cellular Immune Suppressor Activity Resides in Lymphocyte Cell Clusters Adjacent to Granulomata in Human Coccidioidomycosis

Li¹,

Dial²,

Schmelz

et al. 2005

Infect Immun

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The in situ immunologic response in human coccidioidomycosis remains undefined. To explore this further, pulmonary necrotizing coccidioidal granulomata were examined using immunohistochemical staining for lymphocyte subsets and for the cytokines interleukin-10 (IL-10) and gamma interferon (IFN-␥). Discrete perigranulomatous lymphocytic clusters were seen in eight of nine tissues examined. In these tissues, T lymphocytes (CD3 ؉ ) significantly outnumbered B lymphocytes (CD20 ؉ ) in the mantle area of the granulomata (P ‫؍‬ 0.028), whereas the clusters were composed of roughly equal numbers of T and B lymphocytes. While the number of cells in the mantle expressing IL-10 was similar to those in the perigranulomatous clusters, there were significantly more cells expressing IFN-␥ in the mantle than in the clusters (P ‫؍‬ 0.037). Confocal microscopy revealed that CD4؉ T lymphocytes and B lymphocytes are associated with IL-10 production. CD4؉ CD25 ؉ T lymphocytes were identified in the perigranulomatous clusters but were not associated with IL-10 production. This is the first report noting perigranulomatous lymphocyte clusters and IL-10 in association with human coccidioidal granulomata and suggests that down-regulation of the cellular immune response is occurring within coccidioidal granulomata.Coccidioidomycosis is a fungal infection of increasing importance in the southwest United States (4). In the vast majority of cases, infection is acquired by inhalation of the fungus. Two-thirds of individuals who become infected are asymptomatic, their only evidence of infection being the expression of delayed-type hypersensitivity in response to a coccidioidal skin test. A variety of studies have indicated that protective immunity in human coccidioidomycosis is associated with an appropriate cellular immune response. Smith and colleagues demonstrated that persistent expression of delayed-type hypersensitivity presaged a good outcome, while failure to develop this response was associated with disseminated disease (20). More recently, in vitro studies have shown that peripheral blood T lymphocytes from individuals with well-controlled infection produce gamma interferon (IFN-␥) in response to coccidioidal antigen, while cells from individuals with disseminated disease do not (1). Failure of T lymphocytes to react to coccidioidal antigen in vitro is associated with a poorer clinical score among those with disseminated disease (2).The hallmark of a robust T-lymphocyte response is the granuloma (10), and the formation of necrotizing granulomata as a response to pulmonary coccidioidomycosis has long been associated with a strong cellular immune response and control of coccidioidal disease (6). However, the precise immunological events associated with this response have been largely unexplored. Modlin and colleagues, in work published in 1985 (13), described a distinct pattern of cellular response in a single human pulmonary granuloma. In this pattern, CD4 ϩ lymphocytes were dispersed throughout the granuloma, while CD8 ϩ lymphocytes...

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In Vitro Whole-Blood Analysis of Cellular Immunity in Patients with Active Coccidioidomycosis by Using the Antigen Preparation T27K

Cited by 22 publications

References 29 publications

Vaccine Immunity to Coccidioidomycosis Occurs by Early Activation of Three Signal Pathways of T Helper Cell Response (Th1, Th2, and Th17)

Vaccine Immunity to Coccidioidomycosis Occurs by Early Activation of Three Signal Pathways of T Helper Cell Response (Th1, Th2, and Th17)

Spherules Derived from Coccidioides posadasii Promote Human Dendritic Cell Maturation and Activation

Cellular Immune Suppressor Activity Resides in Lymphocyte Cell Clusters Adjacent to Granulomata in Human Coccidioidomycosis

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