Accumulation of Interferon Gamma-Producing TH1 Helper T Cells in Nasal Polyps

1994 ◽  
Vol 111 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Chase H. Miller ◽  
Deborah R. Pudiak ◽  
Fadi Hatem ◽  
Richard J. Looney
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Nasal Polyps ◽  
Interleukin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
T Cell Clones ◽  
Cell Clones ◽  
Polyp Tissue

We investigated the mechanisms involved in the formation of nasal polyps by examining T-cell clones and their production of soluble mediators in nasal polyps. Recently, the allergic origin of nasal polyps has been challenged. To study this question we characterized T cells from polyp tissue of allergic individuals in terms of their cytokine pattern. Nasal polyp T cells were cloned from allergic individuals undergoing polypectomy. Polyp tissue was dispersed enzymatically, and T cells were stimulated with mitogen and interleukin-2. Control T cells were obtained from peripheral blood of nonallergic donors. Cytokine production of interleukin-4 and interferon was then determined by indirect enzyme-linked immunosorbent assay tests. Polyp T-cell clones were found to produce high interferon but low interleukin-4 levels that were not significantly different from control peripheral blood T-cell clones. In addition, immunoglobulin production by dispersed polyp tissue was investigated. Immunoglobulin levels were higher in polyp tissues than in serum with immunoglobulin A predominating. These results suggest that the inflammatory reaction in nasal polyps is different than that seen in a typical type I hypersensitivity response.

scholarly journals An Ex Vivo Study of T Lymphocytes Recovered from the Lungs of I/St Mice Infected with and Susceptible toMycobacterium tuberculosis

1998 ◽  
Vol 66 (10) ◽  
pp. 4981-4988 ◽  
Author(s):  
Irina Lyadova ◽  
Vladimir Yeremeev ◽  
Konstantin Majorov ◽  
Boris Nikonenko ◽  
Sergei Khaidukov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Antimycobacterial Activity ◽  
Enzymatic Digestion ◽  
Interleukin 4 ◽  
T Cell Clones ◽  
Cell Clones ◽  
Ifn Γ

ABSTRACT I/St mice, previously characterized as susceptible toMycobacterium tuberculosis H37Rv, were given 103 or 105 CFU intravenously. At two time points postinoculation, the cell suspensions that resulted from enzymatic digestion of lungs were enumerated and further characterized phenotypically and functionally. Regarding the T-cell populations recovered at 2 and 5 weeks postinfection, two main results were obtained: (i) the population of CD44− CD45RB+cells disappeared within 2 weeks postinfection, while the number of CD44+ CD45RB−/low cells slowly increased between weeks 2 and 5; (ii) when cocultured with irradiated syngeneic splenocytes, these lung T cells proliferated in the presence of H37Rv sonicate. Using H37Rv sonicate and irradiated syngeneic splenocytes to reactivate lung T cells, we selected five CD3+CD4+ CD8− T-cell clones. In addition to the H37Rv sonicate, the five clones react to both a short-term culture filtrate and an affinity-purified 15- to 18-kDa mycobacterial molecule as assessed by the proliferative assay. However, there was a clear difference between T-cell clones with respect to cytokine (gamma interferon [IFN-γ] and interleukin-4 [IL-4] and IL-10) profiles: besides one Th1-like (IFN-γ+ IL-4−) clone and one Th0-like (IFN-γ+ IL-4+IL-10+) clone, three clones produced predominantly IL-10, with only marginal or no IL-4 and IFN-γ responses. Inhibition of mycobacterial growth by macrophages in the presence of T cells was studied in a coculture in vitro system. It was found that the capacity to enhance antimycobacterial activity of macrophages fully correlated with INF-γ production by individual T-cell clones following genetically restricted recognition of infected macrophages. The possible functional significance of cytokine diversity among T-cell clones is discussed.

scholarly journals Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3303-3314 ◽  
Author(s):  
J.H. Richardson ◽  
P. Höllsberg ◽  
A. Windhagen ◽  
L.A. Child ◽  
D.A. Hafler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Leukemia Virus ◽  
Type I ◽  
Cell Leukemia Virus Type ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones ◽  
T Cell Leukemia Virus ◽  
Spontaneous Proliferation

Abstract Human T-cell leukemia virus type I (HTLV-I)-infected T cells expanded in vitro by single-cell cloning provide a unique system for investigating virus-cell interactions in nonimmortalized T cells. By analysis of clones generated randomly from the blood of virus carriers, we confirm that CD4 T cells are the major reservoir of HTLV-I in vivo and show that most infected cells contain a single integrated provirus. Contrary to the situation in HTLV-I immortalized cell lines, the HTLV-I provirus was found to be transcriptionally silent in a high proportion of randomly generated T-cell clones and could not be reactivated by mitogenic stimulation. The spontaneous proliferation previously documented in HTLV-I–infected T-cell clones was not observed in silently infected cells, and therefore correlates directly with the expression of tax and other viral genes. The only cytokine mRNA found to be significantly elevated in the virus-producing clones was interleukin-6; however, receptor-blocking experiments argue against a role for IL-6 in the virus-induced cell proliferation. We observed a striking variation in the ability of individual HTLV-I–producing clones to immortalize fresh peripheral blood lymphocytes. This ability did not correlate with the levels of viral mRNA expression, gag p24 production, spontaneous proliferation, or tax-transactivation, possibly suggesting a role for host cell factors as determinants of viral infectivity or immortalization. Studies to elucidate the basis of this phenotypic heterogeneity should enhance our understanding of viral spread and pathogenesis.

Demonstration of Frequent Occurrence of Clonal T Cells in the Peripheral Blood But Not in the Skin of Patients With Small Plaque Parapsoriasis

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1409-1417 ◽  
Author(s):  
J. Marcus Muche ◽  
Ansgar Lukowsky ◽  
Jürgen Heim ◽  
Markus Friedrich ◽  
Heike Audring ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Clone ◽  
Small Plaque ◽  
Blood Samples ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Clone

Clinical, immunohistological, and molecular biological data suggest the chronic dermatosis small plaque parapsoriasis (SPP) to be a precursor of mycosis fungoides (MF). However, most data are contradictory and confusing due to inexact definition of SPP. Recently, clonal T cells were detected in skin and blood samples of early MF. Because demonstration of identical T-cell clones in skin and blood of SPP patients would indicate a close relationship of SPP to MF, we investigated the clonality of skin and blood specimens from 14 well-defined SPP patients. By a polymerase chain reaction (PCR) amplifying T-cell receptor γ rearrangements and subsequent high-resolution electrophoresis, clonal T cells were detected in 9 of 14 initial and 32 of 49 follow-up blood samples, but in 0 of 14 initial skin specimens. Even a clone-specific PCR showing the persistence of the initial blood T-cell clone in 20 of 20 follow-up samples, failed to detect the T-cell clone in the skin. In 2 patients, the clonal T cells were shown to be CD4+. For the first time, the majority of SPP patients was shown to carry a T-cell clone in the peripheral blood. Although a relation between circulating clonal T cells and SPP cannot directly be proven by the applied techniques, our results indicate blood T-cell clonality to be a characteristic feature of SPP and CTCL because analysis of multiple controls and clinical workup of our SPP patients excluded other factors simulating or causing a clonal T-cell proliferation. A sufficient cutaneous antitumor response but also an extracutaneous origin of the T-cell clones might explain the failure to detect skin infiltrating clonal T cells.

scholarly journals Presence of Oligoclonal T Cells in Cerebrospinal Fluid of a Child with Multiphasic Disseminated Encephalomyelitis following Hepatitis A Virus Infection

2001 ◽  
Vol 8 (5) ◽  
pp. 984-992 ◽  
Author(s):  
Emilia L. Oleszak ◽  
Wan Lu Lin ◽  
Agustin Legido ◽  
Joseph Melvin ◽  
Huntley Hardison ◽  
...  
Keyword(s):  
T Cells ◽  
Cerebrospinal Fluid ◽  
T Cell ◽  
Peripheral Blood ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Clonal Expansion ◽  
T Cell Clones ◽  
Cell Clones ◽  
Β Chain

ABSTRACT We have investigated the clonality of β-chain T-cell receptor (TCR) transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year old child who developed a multiphasic disseminated encephalomyelitis following an infection with hepatitis A virus. We amplified β-chain TCR transcripts by nonpalindromic adaptor (NPA)-PCR–Vβ-specific PCR. TCR transcripts from only five Vβ families (Vβ13, Vβ3, Vβ17, Vβ8, and Vβ20) were detected in CSF. The amplified products were combined, cloned, and sequenced. Sequence analysis revealed in the CSF substantial proportions of identical β-chain of TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of 35 (48%) transcripts were 100% identical, demonstrating a major Vβ13.3 Dβ2.1 Jβ1.3 clonal expansion. Six of 35 (17%) transcripts were also 100% identical, revealing a second Vβ13 clonal expansion (Vβ13.1 Dβ2.1 Jβ1.2). Clonal expansions were also found within the Vβ3 family (transcript Vβ3.1 Dβ2.1 Jβ1.5 accounted for 5 of 35 transcripts [14%]) and within the Vβ20 family (transcript Vβ20.1 Dβ1.1 Jβ2.4 accounted for 3 of 35 transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal expansions in the CSF of this patient following infection with hepatitis A virus. Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell clones exhibited substantial homology to myelin basic protein-reactive T-cell clones. In contrast, all Vβ TCR families were expressed in peripheral blood lymphocytes. Oligoclonal expansions of T cells were not detected in the peripheral blood of this patient. It remains to be determined whether these clonally expanded T cells are specific for hepatitis A viral antigen(s) or host central nervous system antigen(s) and whether molecular mimicry between hepatitis A viral protein and a host protein is responsible for demyelinating disease in this patient.

scholarly journals T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

2001 ◽  
Vol 69 (9) ◽  
pp. 5345-5351 ◽  
Author(s):  
Luiza Guilherme ◽  
Sandra E. Oshiro ◽  
Kellen C. Faé ◽  
Edécio Cunha-Neto ◽  
Guilherme Renesto ◽  
...  
Keyword(s):  
T Cells ◽  
Heart Disease ◽  
T Cell ◽  
Rheumatic Heart Disease ◽  
Peripheral Blood ◽  
Cell Reactivity ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Reactivity ◽  
Rheumatic Heart

ABSTRACT T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). We searched for immunodominant T-cell M5 epitopes among RHD patients with defined clinical outcomes and compared the T-cell reactivities of peripheral blood and intralesional T cells from patients with severe RHD. The role of HLA class II molecules in the presentation of M5 peptides was also evaluated. We studied the T-cell reactivity against M5 peptides and heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesional and peripheral T-cell clones from RHD patients. Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequently recognized by PBMC from RHD patients than by those from controls. The M5 peptide encompassing residues 81 to 96 [M5(81–96) peptide] was most frequently recognized by PBMC from HLA-DR7+DR53+ patients with severe RHD, and 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81–103) region. Heart proteins were recognized more frequently by PBMC from patients with severe RHD than by those from patients with mild RHD. The similar pattern of T-cell reactivity found with both peripheral blood and heart-infiltrating T cells is consistent with the migration of M-protein-sensitized T cells to the heart tissue. Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensitized T cells from the heart lesion.

Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones

Science ◽  
1991 ◽  
Vol 254 (5029) ◽  
pp. 279-282
Author(s):  
P Salgame ◽  
JS Abrams ◽  
C Clayberger ◽  
H Goldstein ◽  
J Convit ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interferon Gamma ◽  
Antibody Formation ◽  
T Cell Subsets ◽  
Interleukin 4 ◽  
Reciprocal Relation ◽  
Cell Mediated Immunity ◽  
T Cell Clones ◽  
Cell Clones

Functional subsets of human T cells were delineated by analyzing patterns of lymphokines produced by clones from individuals with leprosy and by T cell clones of known function. CD4 clones from individuals with strong cell-mediated immunity produced predominantly interferon-gamma, whereas those clones that enhanced antibody formation produced interleukin-4. CD8 cytotoxic T cells secreted interferon-gamma. Interleukin-4 was produced by CD8 T suppressor clones from immunologically unresponsive individuals with leprosy and was found to be necessary for suppression in vitro. Both the classic reciprocal relation between antibody formation and cell-mediated immunity and resistance or susceptibility to certain infections may be explained by T cell subsets differing in patterns of lymphokine production.

scholarly journals Functional expression of B7/BB1 on activated T lymphocytes.

1993 ◽  
Vol 177 (3) ◽  
pp. 845-850 ◽  
Author(s):  
M Azuma ◽  
H Yssel ◽  
J H Phillips ◽  
H Spits ◽  
L L Lanier
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Activated T Cells ◽  
T Cell Clones ◽  
Cell Clones

B7/BB1 is a membrane differentiation antigen expressed on activated B cells, macrophages, and dendritic cells that binds to a counter-receptor, CD28, expressed on T lymphocytes and thymocytes. Interaction between CD28 and B7 results in potent costimulation of T cell activation initiated via the CD3/T cell receptor complex. We now report that B7 is also expressed on activated human peripheral blood T cells, CD4 T cell clones, CD8 T cell clones, and natural killer cell clones. B7 appears relatively late after T cell activation, can be detected on both CD4 and CD8 T cell subsets, and is present on antigen-specific, major histocompatibility complex-restricted CD4 and CD8 T cell clones. Expression of B7 on activated T cells was confirmed by immunoprecipitation from 125I-labeled activated T cells and by detection of B7 transcripts. A B7+ CD4+ T cell clone was able to stimulate a primary allogeneic mixed lymphocyte response using small, resting peripheral blood T cells as responders. The alloantigen-induced proliferative response and cytokine production was partially inhibited by anti-B7 monoclonal antibody. Since activated T cells can coexpress both CD28 and its counter-receptor, B7, this suggests that activated T cells may be capable of autocrine costimulation via the CD28 activation pathway.

scholarly journals Accumulation of Human Heat Shock Protein 60-Reactive T Cells in the Gingival Tissues of Periodontitis Patients

2002 ◽  
Vol 70 (5) ◽  
pp. 2492-2501 ◽  
Author(s):  
Kazuhisa Yamazaki ◽  
Yutaka Ohsawa ◽  
Koichi Tabeta ◽  
Harue Ito ◽  
Kaoru Ueki ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Peripheral Blood ◽  
Cytokine Profile ◽  
T Cell Clones ◽  
Cell Clones ◽  
Ifn Γ ◽  
Human Hsp60

ABSTRACT Heat shock protein 60s (hsp60) are remarkably immunogenic, and both T-cell and antibody responses to hsp60 have been reported in various inflammatory conditions. To clarify the role of hsp60 in T-cell responses in periodontitis, we examined the proliferative response of peripheral blood mononuclear cells (PBMC), as well as the cytokine profile and T-cell clonality, for periodontitis patients and controls following stimulation with recombinant human hsp60 and Porphyromonas gingivalis GroEL. To confirm the infiltration of hsp60-reactive T-cell clones into periodontitis lesions, nucleotide sequences within complementarity-determining region 3 of the T-cell receptor (TCR) β-chain were compared between hsp60-reactive peripheral blood T cells and periodontitis lesion-infiltrating T cells. Periodontitis patients demonstrated significantly higher proliferative responses of PBMC to human hsp60, but not to P. gingivalis GroEL, than control subjects. The response was inhibited by anti-major histocompatibility complex class II antibodies. Analysis of the nucleotide sequences of the TCR demonstrated that human hsp60-reactive T-cell clones and periodontitis lesion-infiltrating T cells have the same receptors, suggesting that hsp60-reactive T cells accumulate in periodontitis lesions. Analysis of the cytokine profile demonstrated that hsp60-reactive PBMC produced significant levels of gamma interferon (IFN-γ) in periodontitis patients, whereas P. gingivalis GroEL did not induce any skewing toward a type1 or type2 cytokine profile. In control subjects no significant expression of IFN-γ or interleukin 4 was induced. These results suggest that periodontitis patients have human hsp60-reactive T cells with a type 1 cytokine profile in their peripheral blood T-cell pools.

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