PubMed Health⌕ Search

Biomedical subjects

K Gott

Publications and source records attributed to K Gott.

At least 19 recordsLinked to original sources
PubMed2004

The role of MIP-1alpha in experimental hypersensitivity pneumonitis.

S. rectivirgula (SR) causes Farmer's Lung Disease, a classic example of hypersensitivity pneumonitis (HP). We utilized a model of experimental hypersensitivity pneumonitis (EHP), antibody to MIP-1alpha and MIP-1alpha -/- mice, to test the hypothesis that MIP-1alpha is essential in the development of EHP. Treatment of C57BI/6 mice with anti-MIP-1alpha antibody did not change the extent of pulmonary histology abnormalities, BALF cell number or characteristics, or BALF concentration of IL12p40, TNF, IL1alpha and IL6, after an i.t. challenge with SR. MIP-1alpha -/- animals responded similarly to wild-type (wt) animals in the extent and nature of pulmonary histologic changes and BALF cell number and type after a single i.t. injection of SR There was a dose-response relationship between the amount of SR and BALF IL12p40, MCP-1 and IL6 in both strains, and MIP-1alpha in wild-type animals. We next transferred SR cultured spleen cells from SR sensitized mice (both wt and MIP-1alpha -/-) to naive recipients. Lung histology and BALF characteristics after SR i.t. challenge of the recipients were used to determine if adoptive transfer had occurred. Cultured cells from MIP-1alpha -/- animals were fully capable of transferring EHP to recipients. There was no difference of BALF TNF, IL6 and IL1alpha between the strains, but there was more MCP-1 and IL12p40 in the MIP-1alpha -/- mice than in the control mice. MIP-1alpha is not necessary for the recruitment of cells into the lung and BALF after i.t. administration of SR, or the development of cells able to adoptively transfer EHP.

Alveolitis, Extrinsic Allergic↗
PubMed2000

Mediators of hypersensitivity pneumonitis.

Inhalation of Saccharopolyspora rectivirgula (S. rectivirgula) causes farmer's lung disease, a classic example of hypersensitivity pneumonitis (HP). HP is characterized by bronchoalveolar lavage fluid (BALF) neutrophilia (within the first 48 hours after inhalation), followed by BALF lymphocytosis. We utilized a well-described murine model of HP to determine the timing of the appearance of the C-C chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha); the inflammatory cytokines tumor necrosis factor (TNF), interleukin-1alpha (IL-1alpha), and interleukin-6 (IL-6); and the Th1 -differentiating cytokine interleukin-12 (IL-12) in BALF. After a single intratracheal administration of S. rectivirgula, there was remarkable BALF neutrophilia (peak 24 to 48 hours), followed by a BALF lymphocytosis (peak 48 to 72 hours) in both C57Bl/6 and BALB/c mice that was preceded by the appearance of MIP-1alpha in BALF (peak 4 to 6 hours) and MCP-1 (peak at 48 hours). In both strains of mice there was a striking increase of BALF IL-12 (peak 48 to 72 hours). There was also an increase in BALF IL-6, IL-1alpha, and TNF that was greater in the BALB/c mice than in the C57Bl/6 mice. S. rectivirgula induced the secretion of MIP-1alpha, MCP-1, IL-6, IL-1alpha, and IL-12 from the murine macrophage cell line J774A.1; MIP-1alpha, IL-6, IL-1alpha, IL-12, and TNF from C57Bl/6 alveolar macrophages; and IL-1alpha, IL-6, and TNF-but not IL-12-from BALB/c alveolar macrophages. We conclude that chemokines and cytokines induced by intratracheal administration of S. rectivirgula precede BALF neutrophilia and lymphocytosis and may cause differentiation of Th1 cells; we also conclude that pulmonary macrophages represent a potential source of these substances.

Alveolitis, Extrinsic Allergic↗
PubMed1999

Th1 cells that adoptively transfer experimental hypersensitivity pneumonitis are activated memory cells.

Cultured murine CD4+ T cell lines from Saccharopolyspora rectivirgula-sensitized donors with cytokine secretion characteristics of Th1 cells can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP), whereas Th2 CD4+ cell lines cannot (Cell Immunol 177:169-175, 1997). To assess the differences between these cell lines that may be related to the ability to transfer EHP, we determined cell surface markers that distinguish naive from activated/memory cells that indicate activation and that mediate endothelial adhesion. Both Th1 and Th2 T cell lines are CD4+, CD11a+, ICAM-1+, and L-selectin negative. Th1 cells are CD49d (alpha 4) and LPAM (alpha 4 beta 7) positive, with 32% and 42% of the apparent membrane site density quantitated as the mean molecules of equivalent soluble fluorochromes (MESF) values of unstimulated spleen cells, respectively. Th2 cells are weakly alpha 4 and alpha 4 beta 7 positive, with 15% and 11% of the MESF of unstimulated spleen cells. Th1 cell lines are CD45Rb negative and CD44+, whereas Th2 cell lines are CD45Rb intermediate and CD44-/low. Th1 cells are CD25 (IL-2 receptor) low and Th2 cells CD25 high. We conclude that Th1 cells capable of transfer are activated/memory T cells, and Th2 cells incapable of transfer lack some characteristics of memory/activated T cells (i.e., increase of CD44 and decrease of CD45Rb). Both Th1 and Th2 cell lines express alpha 4 beta 7 and alpha 4 (Th1 > Th2), suggesting that alpha(4) integrin may be important in conferring ability to cells to adoptively transfer EHP.

Adoptive Transfer↗
PubMed1999

Experimental hypersensitivity pneumonitis: influence of Th2 bias.

Cultured murine CD4+ cells from Saccharopolyspora rectivirgula sensitized C3H/HeJ (Th1 bias) donors can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP). We sensitized BALB/c mice (Th2 bias) with S. rectivirgula, obtained spleen and lung associated lymph node (LALN) cells, cultured the cells with specific antigen, and attempted adoptive transfer of EHP. We also treated both C3H/HeJ and BALB/c donor mice with IL4 and anti-IFNgamma before exposure to S. rectivirgula and then cultured cells from both spleen and LALN before attempted transfer of EHP. We found that cultured spleen and lung associated lymph node cells can adoptively transfer EHP in both C3H/HeJ and BALB/c mice as demonstrated by infiltration of the recipient lungs with CD4+ lymphocytes. Treatment of both mouse strains with IL4 and anti-IFNgamma did not change the ability of cultured cells to adoptively transfer EHP. We conclude that EHP induced by S. rectivirgula can occur in animals with either a Th1 or a Th2 bias and is not altered by treatment with IL4 and anti-IFNgamma. This suggests that attributes of the antigen and not genetic background or cytokine environment at the site of initial sensitization determines the results of exposure to S. rectivirgula.

Adoptive Transfer↗
PubMed1998

Effect of glucan on murine lungs.

Glucan, a folded high-molecular-weight polysaccharide, has multiple effects in animals when administered intravenously or intraperitoneally, but not when administered by inhalation. The hypotheses tested were whether intratracheal administration of glucan can cause lung damage and whether some of the resulting lung injury is immunologically mediated. There was a dose-response relationship between the amount of intratracheally injected glucan and the extent of pulmonary histologic abnormalities, which consisted of peribronchiolar and intraalveolar infiltration with chronic inflammatory cells. An attempt to adoptively transfer increased susceptibility to glucan induced lung injury was made. Cells cultured with glucan were transferred into naive recipients before intratracheal glucan exposure. The extent of pulmonary inflammation that occurred as a result of intratracheal injection of glucan was not affected by transfer of cultured cells from glucan-treated animals. However, high concentrations of glucan in culture did produce cells with the appearance of lymphoblasts. These data indicate that glucan induces lung injury, but that there is no evidence of cell mediation of pulmonary injury induced by intratracheal exposure to glucan.

Animals↗
PubMed1998

Experimental hypersensitivity pneumonitis: location of transferring cells.

Cultured cells from Micropolyspora faeni-sensitized donors can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP). We sought to determine the location of transferred cells in recipient animals, the influence of the origin of the cultured cells, and the effect of specific intratracheal challenge. We labeled cultured sensitized spleen or lung-associated lymph node (LALN) cells with CFDA-SE, a cytoplasmic stain, before transfer to naive recipients, which were sacrificed 1 h, 1 day, or 4 days thereafter. We also transferred labeled cultured spleen cells to recipients that were challenged with intratracheal M. faeni and sacrificed 4 days later (MF). Controls were recipients of M. faeni-sensitized and cultured cells challenged with intratracheal normal saline (NS) and recipients of ovalbumin (OVA)-sensitized cells cultured with M. faeni and challenged with intratracheal M. faeni (OVA). The number and proportion of cells that were stained were determined in dispersed spleen, peripheral and lung-associated lymph nodes, and lung parenchyma. The extent of the pulmonary inflammatory response was measured by determining the proportion of microscopic fields that were abnormal and the total number of dispersed pulmonary cells. CFDA-SE stained cells uniformly, and stained cells could be detected in recipients for up to 7 days after transfer. CFDA-SE treatment (0.5 microM) did not affect the ability of cells to transfer EHP adoptively. Transferred cells could be detected easily in lung, lung-associated and peripheral lymph nodes, blood, and spleen. Transferred cells localized to the lung at 1 h but then rapidly decreased with no difference between labeled cells from spleen and LALN. After intratracheal M. faeni challenge, there was no difference in the proportion of labeled cells in the lung among any of the groups (MF, NS, or OVA). There was an increase in the number of lung cells in the MF group compared with the control (NS and OVA) groups. We conclude that cells capable of transfer are transiently (1 h) trapped in the lung but are much decreased in the lung by four days after transfer. After intratracheal antigen challenge of recipients, there is a substantial increase in the number of pulmonary cells in animals exhibiting adoptive EHP but not in the control groups. Transferred cells responsible for EHP are increased in the lungs of animals with adoptive EHP.

Adoptive Transfer↗
PubMed1997

Th1 CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis.

Cultured cells from Micropolyspora faeni-sensitized donors can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP). To determine whether the CD4+ cells responsible for transfer have characteristics of Th1 or Th2 cells, we established cell lines from lung-associated lymph nodes of M. faeni-sensitized C3H/HeJ mice by culturing with antigen and either IFN-gamma, IL2, and anti-IL4, or IL4. Cell lines were stimulated regularly with antigen, fresh antigen-presenting cells, and the cytokine/anti-cytokine antibody cocktail. At various times after initiation of culture, cells were injected intravenously into recipients, which were then challenged intratracheally with M. faeni and sacrificed and the extent of pulmonary inflammatory response was determined. IFN-gamma, IL4, and IL10 levels were determined in supernatants of cell cultures stimulated with M. faeni to characterize the cell lines as Th1 (IFN-gamma, but low IL4 and IL10 secretion) or Th2 (IL4 and IL10, but low IFN-gamma secretion). Cell lines were differentiated into either Th1 (IFN-gamma = 310 +/- 45 U/ml, IL4 = 0.10 +/- 0.1 U/ml, IL10 = 1750 +/- 75 pg/ ml, >99% CD4+) cell lines by Day 16 of culture or Th2 cell lines (IFN-gamma = 1.8 +/- 1.0 U/ml, IL4 = 830 +/- 388 U/ml, IL10 = 51,700 +/- 10,900 pg/ml, >96% CD4+) by Day 30. Th1 cell lines were able to adoptively transfer EHP whereas Th2 cell lines were unable to adoptively transfer EHP. The ability to transfer EHP was directly related to the amount of IFN-gamma and inversely to the amount of IL4 secreted by antigen-stimulated cells. We conclude that it is possible to produce CD4+ cell lines with either Th1 or Th2 characteristics from lung-associated lymph nodes of mice exposed to M. faeni and that only Th1 CD4+ cell lines can adoptively transfer EHP.

Adoptive Transfer↗
PubMed1996

alpha(1,3)Fucosyltransferase expression in E-selectin-mediated binding of gastrointestinal tumor cells.

E-selectin recognizes the oncofetal antigen sialyl-Lewis X, which is highly expressed in adenocarcinoma. Five alpha(1,3)fucosyltransferases (FT) have been cloned that confer cell-surface expression of sialyl-Lewis X on transfected cells. We show here that 12/18 gastrointestinal-tumor cell lines bind specifically to immobilized E-selectin and that in sialyl-Lewis-X-positive cells binding is inhibited with a monoclonal antibody against sialyl-Lewis X. Using RT-PCR, we determined the expression of the alpha(1,3)fucosyltransferases III, IV, V, VI and VII in gastrointestinal tumor cells. Transcripts of FT IV and FT VII are abundantly expressed in all tested cells. Therefore no single fucosyltransferase could be correlated with the expression of sialyl-Lewis X and the ability of the tumor cells to bind to E-selectin. The data suggest that in gastrointestinal-tumor cells sialyl-Lewis X is necessary but not sufficient for E-selectin binding.

Base Sequence↗
PubMed1996

Experimental hypersensitivity pneumonitis: cellular requirements.

We previously demonstrated that Thy1.2+, CD4+, Ia-T cells are responsible for transfer of murine adoptive experimental hypersensitivity pneumonitis (adoptive EHP). To characterize the culture conditions necessary for development of these cells, we depleted cell cultures of Thy1.2+, CD4+, CD8+, or Ia+ cells using MoAbs and complement or magnetic beads, prior to culture of sensitized C3H/HeJ murine spleen cells (SC) with Micropolyspora faeni. After culture, cells were transferred to recipients which were later challenged intratracheally with M. faeni. The extent of pulmonary inflammatory changes in these animals was determined 4 days after intratracheal (i.t.) challenge with M. faeni. Cultured M. faeni-sensitized SC which had been treated before culture with media, complement only, anti-CD8 plus complement or magnetic beads alone could transfer EHP to naive animals. SC treated with anti-Thy1.2 or anti-CD4 plus complement could not transfer EHP. Treatment of SC with anti-Iak plus magnetic beads diminished the ability of cultured cells to transfer EHP. We conclude that the ability to produce cells able to adoptively transfer EPH is dependent on the presence of Thy1.2+, CD4+, and Ia+ cells, but not CD8+ cells, at the onset of culture.

Alveolitis, Extrinsic Allergic↗
PubMed1996

Post-transplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient.

Post-transplantation lymphoproliferative disorder (PTLD) is a widely recognized and often catastrophic complication of organ transplantation. The incidence of PTLD after lung transplantation ranges from 6.2 to 9.4% and is two-fold higher than that seen after organ transplantation of other organs. Primary Epstein-Barr virus (EBV) infection is a major risk factor for PTLD, but the incidence of PTLD in EBV seronegative (EBV-) patients seems to vary with type of organ transplant. The goal of this study was to quantify the risk of PLTD based on pre-lung transplantation EBV serostatus in lung transplant patients. Pre- and post-lung transplant serostatus was defined in 80 patients, and our six cases of PTLD occurred in this group. Six of 94 lung transplant patients (6.4%) who survived > 1 mo developed PTLD. All cases of PTLD involved thoracic structures at presentation and occurred in the first post-operative year. Patients who were EBV- before lung transplant were much more likely to develop PTLD than those who were seropositive (EBV+) (five of 15 [33%] versus one of 60 [< 2%], p < 0.001). Consistent with the prevailing adult (donor) EBV+ rate (85%), two of our EBV-patients remained EBV-after lung transplant. Therefore, the rate of PTLD was 42% in those with primary EBV infection. As compared with EBV-patients that remained tumor-free, those who developed PLTD had similar levels of immunosuppressants and doses of anti-viral therapy. We conclude that PLTD occurs predominantly in EBV-naïve patients (risk approximately 1/3). EBV-patients should be monitored more closely after lung transplantation and, possibly, managed with lower immunosuppression. Our data also suggest that anti-viral therapy alone does not decrease the incidence of PTLD in high risk patients, PTLD can be successfully treated in most cases, and EBV-naïve patients should not be excluded from lung transplant because their risk of death from PTLD is < 15%.

Adolescent↗
PubMed1995

Experimental hypersensitivity pneumonitis: effect of Thy1.2+ and CD8+ cell depletion.

We previously demonstrated that recipient CD4+ cells are necessary for expression of adoptive murine experimental hypersensitivity pneumonitis (EHP). In contrast, the acute inflammatory response to intratracheal (i.t.) administration of Micropolyspora faeni (direct EHP) is not CD4+ cell dependent (Am. J. Respir. Crit. Care Med. 1994;149:1286-1294). To further characterize the cells responsible for development of pulmonary inflammation in recipient animals, we depleted recipients of either Thy1.2+ or CD8+ cells before transfer of M. faeni-sensitized cultured C3H/HeJ spleen cells and i.t. challenge with M. faeni. We used the same depletion technique to determine the contribution of these cells to the pulmonary response to i.t. M. faeni in animals that did not receive cultured cells (direct EHP). The nature and extent of pulmonary inflammatory changes in these animals were assayed either 4 d after i.t. challenge with M. faeni in adoptive EHP or 2 d after i.t. challenge with M. faeni in direct EHP. We also tested the hypothesis that our previously demonstrated ablation of adoptive EHP caused by administration of anti-CD4 antibody was due to depletion of recipient CD4+ cells by allowing recovery of recipient CD4+ cells of anti-CD4-treated animals before i.t. challenge. In addition, we allowed Thy1.2+ cell recovery of anti-Thy1.2-treated animals before i.t. challenge. Cultured M. faeni-sensitized spleen cells could adoptively transfer EHP to animals treated with an irrelevant antibody or PBS. Depletion of Thy1.2+ but not CD8+ cells ablated the ability of recipient animals to express adoptive EHP. Direct EHP was not affected by depletion of Thy1.2+ or CD8+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1995

Experimental hypersensitivity pneumonitis: in vitro effects of interleukin-2 and interferon-gamma.

Cultured CD4+ cells are responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis (EHP) (ARRD 1992; 146:1582-8). To characterize interactions that occur in vitro that result in cells able to transfer EHP, we added either antibody to IFN-gamma, antibody to IL-2, or 30 or 300 micrograms/ml IFN-gamma at the onset of 72-hour culture of C3H/HeJ spleen cells from either M. faeni or ovalbumin (control) sensitized donors with 30 micrograms/ml Micropolyspora faeni. We determined the phenotype of cells after culture and the amount of IL-2 or IFN-gamma in the culture supernatants, transferred cells to naive recipients, challenged the recipients intratracheally with M. faeni, and determined the extent of pulmonary inflammatory changes 4 days thereafter. Substantial amounts of IL-2 and IFN-gamma were detected in supernatants of cultures from M. faeni-sensitized animals, and lesser amounts were detected in culture supernatants from ovalbumin-sensitized donors. Treatment of cultures of M. faeni-sensitized cells with antibody to IL-2 or IFN-gamma blocked or reduced measurable IL-2 or IFN-gamma for the duration of culture. Treatment with IFN-gamma blocked increased levels of IL-2 at 48 and 72 hours of culture. Cultured M. faeni-sensitized cells adoptively transfer EHP. Cells from cultures depleted of either IL-2 or IFN-gamma or supplemented with IFN-gamma could transfer EHP equally well. We conclude that in vitro maturation of cells capable of adoptive EHP is not dependent on soluble IL-2 or IFN-gamma and is not altered by exogenous IFN-gamma.

Alveolitis, Extrinsic Allergic↗
PubMed1994

Experimental hypersensitivity pneumonitis. Effect of CD4 cell depletion.

We previously demonstrated that Thy1.2+, CD4+, Ia-T cells are responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis (adoptive EHP). To characterize the cells responsible for development of pulmonary inflammation in the recipient animals, we depleted recipients of CD4+ cells using monoclonal antibody GK1.5 before administration of Micropolyspora faeni-sensitized cultured C3H/HeJ spleen cells (SC) and intratracheal (i.t.) challenge with M. faeni. We also used the same depletion technique to determine the contribution of these cells to the pulmonary response to i.t. M. faeni in animals that did not receive cultured cells (direct EHP). The nature and extent of pulmonary inflammatory changes in these animals were assayed either 4 days after i.t. challenge with M. faeni in adoptive EHP or 2 days after i.t. challenge with M. faeni in direct EHP. Cultured M. faeni-sensitized SC could transfer EHP to naive animals or those treated with an irrelevant antibody. Depletion of CD4+ cells ablated the ability of recipient animals to express adoptive EHP. Two days after i.t. M. faeni (direct EHP), there was extensive neutrophilic infiltration of the lung that was not affected by depletion of CD4+ cells. We conclude that the ability to express adoptive EHP is dependent on the presence of CD4+ cells. In contrast, the acute inflammatory response to M. faeni is not CD4+ cell dependent.

Alveolitis, Extrinsic Allergic↗
PubMed1994

Adoptive transfer of experimental hypersensitivity pneumonitis: CD4+ cells are memory and naive cells.

We previously demonstrated that CD4+ cells are responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis. To further characterize the CD4+ cells as naive or memory cells, we depleted Micropolyspora faeni-sensitized cultured C3H/HeJ spleen cells of surface IgM+ cells by panning and Ia+ cells by lysis. We measured the proportion of CD4+ cells that expressed CD45RB, CD44 or LECAM-1 (markers used to distinguish memory from naive CD4+ cells) in spleen cell populations able to transfer experimental hypersensitivity pneumonitis (M. faeni sensitized and cultured) and those unable to transfer experimental hypersensitivity pneumonitis (ovalbumin sensitized and M. faeni cultured). Planning reduced the proportion of B cells from 53% to 11% and of Ia+ cells from 54% to 11%. Further lysis of Ia+ cells from the SIgM(+)-depleted population reduced Ia+ cells to 6%. Thy1+ cells increased from 26% to 55% after panning and to 72% after Ia+ cell lysis. Cultured M. faeni-sensitized spleen cells could transfer experimental hypersensitivity pneumonitis. Depletion of SIgM+ cells enhanced and depletion of Ia+ cells did not affect the capacity to transfer experimental hypersensitivity pneumonitis. The CD4+ cells from M. faeni-sensitized animals were 47% CD45RBhi, 36% CD44+ and 0% LECAM-1hi before culture with M. faeni and 48% CD45RBhi. They were 34% CD44+ and 27% LECAM-1hi after culture. The origin of the cells (from M. faeni- or ovalbumin-sensitized animals) did not affect the phenotype of the CD4+ cells, either before or after culture with M. faeni. We conclude that the active cells in spleen cell cultures are SIgM-, Ia-, CD4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

CD5-negative cell mediated experimental hypersensitivity pneumonitis.

Experimental hypersensitivity pneumonitis (EHP) can be transferred to Strain 2 guinea pigs by peripheral lymph node (PLN) cells cultured in vitro with antigen. The phenotype of the active cells has not been delineated. In addition, it is not known if cultured lung-associated lymph node (LALN) cells can transfer EHP. PLN and LALN cells from donor animals were cultured with a soluble extract of Micropolyspora faeni (10 micrograms/ml), and blast cells were isolated by centrifugation over Percoll gradients. Cultured PLN cells were passed through nylon wool columns, and the adherent and nonadherent fractions were tested for their ability to transfer EHP. PLN blast cell populations were depleted of CD5+ cells by treatment with monoclonal anti CD5 antibody (8BE6) and complement. Syngeneic recipients received media or LALN or PLN blast cells treated with antibody plus complement, media, or complement intravenously. Recipients were challenged intratracheally with M. faeni 48 h after the cell transfer, and they were killed 4 days later. The nonadherent PLN cell population was enriched for CD5+ (T) cells and depleted of surface immunoglobulin-positive (SIg+) cells. Treatment of the PLN blast cell population with 8BE6 and complement decreased CD5+ cells from 25 to 4% and increased SIg+ cells from 62 to 80%. All animals were maintained in HEPA-filtered air. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. There was a low level of pulmonary response to an intratracheal challenge of M. faeni in media recipients. There was a substantial increase (p less than 0.01) of the extent of pulmonary abnormalities in the animals receiving cultured PLN cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1992

CD3+ and CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis.

To characterize the cells responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis (EHP), we depleted Micropolyspora faeni (M. faeni)-sensitized C3H/HeJ spleen cell (SC) cultures of CD3+, CD4+, or CD8+ cells before administration to recipients. We determined the length of time sensitization persists, the ability of cultured lung-associated lymph node (LALN) cells to transfer EHP, and the ability of cultured SC from animals subjected to two, four, or eight weekly intratracheal challenges of M. faeni to transfer EHP. The extent of pulmonary inflammatory response after challenge with intratracheal M. faeni was used to determine adoptive transfer. Depletion reduced the proportion of CD3+ cells from 21 to 1%, CD4+ cells from 15 to 3%, and CD8+ cells from 7 to 1% in the cultured SC population. The proportion of B cells exhibited reciprocal changes. Cultured SC could transfer EHP. Depletion of CD3+ and CD4+, but not CD8+ cells, ablated or diminished the capacity to transfer EHP. Sensitized cells persisted in recipients for at least 8 wk. Cultured LALN cells could transfer EHP. Recipients of cultured SC from 4- and 8-wk donors exhibited less extensive pulmonary abnormalities than recipients of cultured SC from 2-wk donors. The proportion of CD3+, CD4+, CD8+, B cells, and macrophages was the same in cultured cells from 2-, 4-, and 8-wk donors. We conclude that the active cells in SC cultures are CD3+, CD4+, and CD8- T cells, and there are differences in the ability of cultured cells to adoptively transfer EHP that are dependent on the nature of the donor but not on the phenotype of the cell population.

Alveolitis, Extrinsic Allergic↗