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PubMed1979

Limiting dilution analysis of alloantigen-reactive T lymphocytes. III. Effect of priming on precursor frequencies.

The effect of specific priming with alloantigens on the frequency of cytolytic T lymphocyte precursors (CTL-P) has been investigated. Alloimmune lymphoid cells were obtained from the spleen of C57BL/6 (H-2b) mice primed with DBA/2 (H-2d) tumor cells or from 14-day unidirectional mixed leukocyte cultures (C57BL/6 anti-DBA/2). CTL-P frequencies directed against H-2d alloantigens were estimated by limiting dilution analysis in a sensitive micro MLC system. Under these conditions, an apparent increase of 3 to 4-fold in CTL-P frequency was observed in alloimmune (as compared with normal) C57BL/6 spleen cells. Evidence was obtained suggesting that this increase was specific for the priming alloantigens. A much greater increase in CTL-P frequency (25 to 100-fold) was observed after alloimmunization of C57BL/6 spleen cells in unidirectional MLC. Under the latter conditions, 5 to 20% of the surviving splenic MLC cells could be identified operationally as CTL-P. A similar enrichment in CTL-P frequency was obtained when lymph node, peripheral blood, or thymus cells were cultured for 14 days in MLC. These studies provide direct evidence that the pool of specific CTL-P can be expanded after alloimmunization. Furthermore, the very high frequencies observed after in vitro priming indicate that this system should be particularly useful for future studies of the progeny of individual CTL-P.

Animals↗

PubMed2003

Formation of estrone and estradiol from estrone sulfate by normal breast parenchymal tissue.

The study was designed to determine the process and limitations by which estrone sulfate may be a precursor of estradiol in the parenchymal cells of the normal breast. The concentration of estrone sulfate in breast nipple aspirate fluid was 1000-fold greater than that of estradiol. Concentrations of 3H-estrone sulfate in parenchymal cells were only 0.20-0.33 times that of the 1.0 nM concentration in the medium, while 3H-estrone achieved concentrations up to 24 times that in the medium at 37 degrees C. Nevertheless, estrone sulfate added to the medium was linearly converted within a 1000-fold concentration range to estrone in intact cells with a mean half-time of conversion of 628 min per 10(6) cells. Homogenized cells had a half-time of 246 min per 10(6) cells. Thus, the time for entry of estrone sulfate into cells reduced the rate by approximately 55%. In split samples, the Vmax values (+/- S.D.) for intact and homogenized cells were 12.6 +/- 1.4 and 18.3 nmol/h mg DNA, respectively (P<0.03). The corresponding Km values for intact and homogenized cells were 6.0 +/- 1.1 and 4.7 +/- 1.0 microM. Conversion of estrone sulfate to estradiol was more efficient in intact cells than in homogenates with mean half-times of 2173 and 7485 min per 10(6) cells, respectively. Conversion of estrone to estrone sulfate did not occur in these cells despite sulfonation of estrone by MCF-7 breast cancer cells under identical conditions. It is concluded that estrone sulfate can serve as a precursor for estradiol in normal breast tissue. Conversion of estrone to estradiol is a limiting step in the process.

Adult↗

PubMed1982

Precursor frequency analysis of lymphokine-secreting alloreactive T lymphocytes. Dissociation of subsets producing interleukin 2, macrophage-activating factor, and granulocyte-macrophage colony-stimulating factor on the basis of Lyt-2 phenotype.

The frequencies of precursors of C57BL/6 T lymphocytes that respond to DBA/2 alloantigens by secreting the lymphokines interleukin 2 (IL-2), macrophage-activating factor (MAF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been directly compared with cytolytic T lymphocyte precursor (CTL-P) frequencies in limiting dilution microcultures established from spleen cells positively or negatively selected on the basis of Lyt-2 phenotype. A clear dichotomy was observed between CTL-P, which were contained in the Lyt-2+ fraction, and precursors of IL-2-secreting cells, which were detected almost exclusively in the Lyt-2- population. In contrast, precursors of cells secreting MAF and GM-CSF were found in both populations: almost all responding cells from the Lyt-2- fraction produced both these factors, whereas the precursor frequency of MAF-secreting and GM-CSF-secreting cells was three- to fourfold lower in the Lyt-2+ population. These frequency data were consistent with quantitative differences observed in the average production of these lymphokines by Lyt-2+ and Lyt-2- populations.

Animals↗

PubMed1986

Separation and analysis of subcellular organelles in a human promyelocytic leukemia cell line, HL-60: application to the study of myeloid lysosomal enzyme synthesis and processing.

We describe a system for analysis of the intracellular pathways in the biosynthesis and packaging of functionally important proteins in human myeloid cells. The human promyelocytic cell line HL-60 was used since peripheral blood neutrophils are terminally differentiated and do not actively synthesize protein. Cells were disrupted by nitrogen cavitation and subcellular organelles in postnuclear supernatant separated on a discontinuous gradient of Percoll modified to resolve organelles important in protein synthesis. This Percoll gradient separated azurophilic granules from less dense organelles and partially separated the less dense organelles from one another. Approximate densities of organelles identified by electron microscopy and by biochemical markers are azurophilic granules, 1.102 g/mL; endoplasmic reticulum, 1.039 g/mL; Golgi apparatus, 1.032 g/mL; and plasma membrane, 1.027 g/mL. We validated the utility of this method of subcellular fractionation by examining intracellular transport of myeloperoxidase, a myeloid lysosomal enzyme present in azurophilic granules. The subunits of mature myeloperoxidase (molecular weight [mol wt] = 59,000 and 13,500) cosediment with biochemical markers for lysosomes, whereas the large-mol wt (89,000) precursor forms cosediments with biochemical markers of less dense organelles. Within the limits of assay sensitivity, the 89,000-mol wt precursor is enzymatically inactive and has no spectral evidence for a heme group, suggesting that precursors of myeloperoxidase may undergo proteolytic maturation in a prelysosomal compartment with concomitant incorporation of a heme group and acquisition of enzymatic activity. This system of analysis should be suitable for the identification, subcellular localization, and maturational analysis of other myeloid lysosomal enzymes as well as functionally important membrane proteins.

Bone Marrow↗

PubMed1998

Heterogeneity among muscle precursor cells in adult skeletal muscles with differing regenerative capacities.

Skeletal muscle has a remarkable capacity to regenerate after injury, although studies of muscle regeneration have heretofore been limited almost exclusively to limb musculature. Muscle precursor cells in skeletal muscle are responsible for the repair of damaged muscle. Heterogeneity exists in the growth and differentiation properties of muscle precursor cell (myoblast) populations throughout limb development but whether the muscle precursor cells differ among adult skeletal muscles is unknown. Such heterogeneity among myoblasts in the adult may give rise to skeletal muscles with different regenerative capacities. Here we compare the regenerative response of a masticatory muscle, the masseter, to that of limb muscles. After exogenous trauma (freeze or crush injuries), masseter muscle regenerated much less effectively than limb muscle. In limb muscle, normal architecture was restored 12 days after injury, whereas in masseter muscle, minimal regeneration occurred during the same time period. Indeed, at late time points, masseter muscles exhibited increased fibrous connective tissue in the region of damage, evidence of ineffective muscle regeneration. Similarly, in response to endogenous muscle injury due to a muscular dystrophy, widespread evidence of impaired regeneration was present in masseter muscle but not in limb muscle. To explore the cellular basis of these different regenerative capacities, we analyzed the myoblast populations of limb and masseter muscles both in vivo and in vitro. From in vivo analyses, the number of myoblasts in regenerating muscle was less in masseter compared with limb muscle. Assessment of population growth in vitro indicated that masseter myoblasts grow more slowly than limb myoblasts under identical conditions. We conclude that the impaired regeneration in masseter muscles is due to differences in the intrinsic myoblast populations compared to limb muscles.

Animals↗

PubMed2005

Sequence tag scanning: a new explorative strategy for recognition of unexpected protein alterations by nanoelectrospray ionization-tandem mass spectrometry.

Protein analysis by database search engines using tandem mass spectra is limited by the presence of unexpected protein modifications, sequence isoforms which may not be in the protein databases, and poor quality tandem mass spectrometry (MS/MS) of low abundance proteins. The analysis of expected protein modifications can be efficiently addressed by precursor ion scanning. However, it is limited to modifications that show such a characteristic loss in a peptide independent manner. We observed that proline and aspartic acid induced backbone fragmentation is accompanied by a low intensity signal for loss of H3PO4 for several pSer- or pThr-phosphopeptides. We describe here the use of peptide-specific fragments that can be used after a protein was identified to allow in-depth characterization of modifications and isoforms. We consider high abundance fragments formed by cleavage at the C-terminal side of aspartic acid, at the N-terminal side of proline and low mass ions such as a2, b2, b3, y1, y2, and y3. The MS/MS dataset is filtered for each sequence tag of interest by an in silico precursor ion scan. The resulting extracted ion traces are then combined by multiplication to increase specificity. Since the strategy is based on common peptide segments which are shared by different isoforms of peptides it can be applied to the analysis of any post-translational modification or sequence variants of a protein. This is demonstrated for the cases of serine and threonine phosphorylation, histone H1 acetylation and the spotting of multiple H1 isoforms.

Acetylation↗

PubMed1989

Stereochemistry of RNA cleavage by the Tetrahymena ribozyme and evidence that the chemical step is not rate-limiting.

The intervening sequence of the ribosomal RNA precursor of Tetrahymena is a catalytic RNA molecule, or ribozyme. Acting as a sequence-specific endoribonuclease, it cleaves single-stranded RNA substrates with concomitant addition of guanosine. The chemistry of the reaction has now been studied by introduction of a single phosphorothioate in the substrate RNA at the cleavage site. Kinetic studies show no significant effect of this substitution on kcat (rate constant) or Km (Michaelis constant), providing evidence that some step other than the chemical step is rate-limiting. Product analysis reveals that the reaction proceeds with inversion of configuration at phosphorus, consistent with an in-line, SN2 (P) mechanism. Thus, the ribozyme reaction is in the same mechanistic category as the individual displacement reactions catalyzed by protein nucleotidyltransferases, phosphotransferases, and nucleases.

Animals↗

PubMed1982

Functionally distinct helper T cells enriched under different culture conditions cooperate with different B cells.

Helper T cells selected from KLH-primed lymph node cells under different in vitro conditions were analyzed for the ability to cooperate in secondary hapten-specific antibody responses. It is shown that carrier-specific, MHC-restricted helper T cells selected in low-density cultures cooperate with equal efficiency in either PC-specific or DNP-specific responses. In the presence of both PC-specific and DNP-specific B precursors, however, such T cells are limited to participate in only one helper event in vitro. In contrast, the predominant helper T cell in a second population maintained in high-density lymph node cultures cooperates, presumably through a soluble factor, with multiple B precursors. These properties correspond to those previously described for specific and nonspecific effector functions. The experiments reported here further demonstrate that different B cells respond in vitro to carrier-specific and nonspecific helper signals.

Animals↗

PubMed1983

Antigenically activated helper T cells are required as stimulator cells for optimal activation of cytotoxic T lymphocytes under conditions of limiting helper factors.

This paper deals with the question of how antigenically activated helper cells interact with cytotoxic T-lymphocyte (CTL) precursor cells in an environment where helper factor is limiting. Experiments in culture systems with limiting concentrations of helper factor indicated that the (optimal) activation of CTL required antigenically activated helper T cells as stimulator cells. These experiments were performed partly in macrocultures which contained prostaglandin E2 (PGE2) and partly in microcultures with small numbers of responder cells and without additional helper factors. The results showed that a strong activation of CTL against TNP-haptenated syngeneic or semiallogeneic cells occurred only if the cultures contained TNP-haptenated stimulator cells from euthymic but not athymic donors and if the haptenated stimulator cells were exposed to allogeneic determinants. Moreover, combinations of F1-hybrid stimulator cells and parental responder cells generated no substantial cytotoxic responses against determinants of the other parent, unless the cultures were supplemented with a source of I-region determinants which were foreign to the semiallogeneic stimulator cells. Strong responses against haptenated syngeneic or semiallogeneic stimulator cells were obtained, however, when helper factors were added to the cultures. It was concluded that our cultures with limiting concentrations of helper factors required a close proximity between helper T cells and CTL precursor cells; and this proximity was obviously provided by the receptors of the CTL precursor cells with no detectable contribution from the helper-T-cell receptors. Allogeneically activated helper T cells in the responder cell population or in a second irradiated spleen cell population which did not bear the target antigens delivered no substantial helper effect to the CTL precursor cells under test.

Animals↗

PubMed2000

Extent and zonal distribution of prostatic intraepithelial neoplasia in patients with prostatic carcinoma in Japan: analysis of whole-mounted prostatectomy specimens.

BACKGROUND: Prostatic intraepithelial neoplasia (PIN), an intraluminar proliferation of epithelial cells in ducts and acini, is divided into high-grade (HGPIN) and low-grade (LGPIN), based on morphologies. HGPIN is considered to be a putative precursor of prostatic adenocarcinoma (PCA). Information on PIN has been limited in Japan, because PIN had not been regarded as a precursor lesion for PCA. METHODS: In this study, extent and zonal distribution of PIN together with its relationship with PCA were examined in totally embedded radical prostatectomy specimens obtained from 70 patients with PCA. Fifty-three patients received androgen deprivation therapy (castrated) and remaining 17 did not (noncastrated). RESULTS: Frequency of HGPIN in noncastrated cases (76%) was much higher than that in castrated cases (26%) (P < 0.001). LGPIN showed the same tendency, but the difference was smaller. Difference in mean number of HGPIN in noncastrated and castrated cases (12.0 and 6.4, respectively) was more marked than in LGPIN (6.4 and 5.1, respectively). Reduction rate of mean size in HGPIN (26%) by the androgen deprivation therapy was larger than in LGPIN. When evaluated in noncastrated cases, the coexistence of PCA and HGPIN was found in 76% of cases in the nontransition and 53% in the transition zone. Close association of PCA and PIN (</=2 mm distance between lesions) was more frequently found in HGPIN (55% of lesions) than in LGPIN (37%) (P < 0.05). Frequency of close association of HGPIN with PCA was 65% in the nontransition and 35% in transition zone. CONCLUSIONS: The present study from Japan supports the etiological importance of HGPIN in the development of PCA. The effect of androgen deprivation therapy is much more marked in HGPIN than in LGPIN.

Adenocarcinoma↗

PubMed1987

Effect of human recombinant interleukin (IL-2) on peripheral blood mononuclear cells of burned patients.

Interleukin-2 (IL-2) has been suggested to play a key role in the immune response. To investigate the effect of human recombinant IL-2 on proliferative and cytotoxic responses in burn patients, peripheral blood mononuclear cells from 20 severely burned patients (body surface area (BSA) greater than 20 per cent) were studied in this way. Proliferative response measured by tritiated thymidine uptake was impaired from week 2 following injury. IL-2-activated cytotoxicity to NK-resistant target T24 was significantly impaired from week 2. To clarify if the defect in cytotoxic response is due to a decreased number of cell precursors or due to reduced responsiveness to IL-2, a limiting dilution assay was introduced. However, there was no reduction in precursor cell numbers. These data suggest that, in addition to impaired IL-2 production, there is an endogenous defect in IL-2 responsiveness. This may be of clinical importance since it is not possible to reverse this defect, at least in vitro.

Adolescent↗

PubMed2000

Niacin protects the isolated heart from ischemia-reperfusion injury.

Nicotinic acid (niacin) has been shown to decrease myocyte injury. Because interventions that lower the cytosolic NADH/NAD(+) ratio improve glycolysis and limit infarct size, we hypothesized that 1) niacin, as a precursor of NAD(+), would lower the NADH/NAD(+) ratio, increase glycolysis, and limit ischemic injury and 2) these cardioprotective benefits of niacin would be limited in conditions that block lactate removal. Isolated rat hearts were perfused without (Ctl) or with 1 microM niacin (Nia) and subjected to 30 min of low-flow ischemia (10% of baseline flow, LF) and reperfusion. To examine the effects of limiting lactate efflux, experiments were performed with 1) Ctl and Nia groups subjected to zero-flow ischemia and 2) the Nia group treated with the lactate-H(+) cotransport inhibitor alpha-cyano-4-hydroxycinnamate under LF conditions. Measured variables included ATP, pH, cardiac function, tissue lactate-to-pyruvate ratio (reflecting NADH/NAD(+)), lactate efflux rate, and creatine kinase release. The lactate-to-pyruvate ratio was reduced by more than twofold in Nia-LF hearts during baseline and ischemic conditions (P < 0.001 and P < 0.01, respectively), with concurrent lower creatine kinase release than Ctl hearts (P < 0.05). Nia-LF hearts had significantly greater lactate release during ischemia (P < 0.05 vs. Ctl hearts) as well as higher functional recovery and a relative preservation of high-energy phosphates. Inhibiting lactate efflux with alpha-cyano-4-hydroxycinnamate and blocking lactate washout with zero flow negated some of the beneficial effects of niacin. During LF, niacin lowered the cytosolic redox state and increased lactate efflux, consistent with redox regulation of glycolysis. Niacin significantly improved functional and metabolic parameters under these conditions, providing additional rationale for use of niacin as a therapeutic agent in patients with ischemic heart disease.

Animals↗

PubMed1991

The maintenance of lytic specificity during the development of clones of cytotoxic T lymphocytes from single precursor cells.

A high-cloning efficiency, filler cell-free limit-dilution culture system for the growth and differentiation of single cytotoxic T lymphocyte precursors (CTLp) was tested for its ability to maintain the lytic specificity of the resultant clones of cytotoxic T lymphocytes (CTL). The system used non-specific stimulation with phorbyl ester and calcium ionophore, maintenance of growth over the first 6 days of culture with interleukin (IL)-2 and interferon-gamma, and maintenance of growth and differentiation over the last 2 days of culture with IL-2 and IL-6. Under these defined conditions around 50% of all CD4- 8+ T cells developed into CTL clones that were specific in their lytic activity. In contrast, a culture system maintained by irradiated filler cells showed non-specific lysis of both YAC-1 type natural killer targets and of P815 type targets, while a culture system maintained by IL-2 and a crude growth factor preparation showed non-specific lysis of natural killer targets but not of P815. The defined lymphokine culture system was suitable for determining the specificity repertoire of primary CTLp. Using this system, the frequency of reactivity with allogenic tumor targets was found to be approximately one CTLp in 30 for several mouse strain/target cell combinations.

Animals↗

PubMed2000

Characterization of parameters for in vitro culture of isolated ovarian follicles of greenback flounder Rhombosolea tapirina.

Isolated ovarian follicles of greenback flounder Rhombosolea tapirina were incubated with a variety of gonadotropins (GtHs) and steroid precursors for periods of up to 42 h, and levels of free and glucuronated testosterone (T) and 17beta-estradiol (E(2)) in the medium, and free T and E(2) from inside follicles were measured by RIA. Short incubations (6 h) generated increases in T and E(2) in response to steroid precursors, but not human chorionic GtH (hCG), or salmon or carp GtH. At incubation times of 18 h, all GtHs stimulated T and, or E(2) production, whereas after 42-h incubation, GtH effects on E(2) production had disappeared. Steroid precursors remained effective at 18 and 42 h. T and E(2) glucuronides were formed in small quantities but did not account for loss of treatment effects at long incubation times. Instead, this could be explained by accumulation of E(2) in controls as a result of continued basal steroid production. Follicles absorbed substantial amounts of both endogenous and exogenous steroid from the medium, however, this did not appear to have any influence on changes in treatment effects with incubation time. Flounder follicles were most sensitive to hCG, followed by salmon and carp GtH at approximately 10-fold higher concentrations. Ovarian segments were not sensitive to any GtH but did convert exogenous steroid precursors indicating that tissue access by GtH may be a limiting factor under certain in vitro conditions. HCG augmented the conversion of 17-hydroxyprogesterone (17P) to T but not T to E(2), consistent with the relative GtH-insensitivity of aromatase in other species. Follicles converted a range of steroid precursors with equal competence, indicating that no step in the cleavage pathway is strongly rate-limited, and that choice of precursor is unlikely to affect the assessment of steroidogenic activity.

17-alpha-Hydroxyprogesterone↗

PubMed2002

Estimating the precursor frequency of naive antigen-specific CD8 T cells.

The constraint of fitting a diverse repertoire of antigen specificities in a limited total population of lymphocytes results in the frequency of naive cells specific for any given antigen (defined as the precursor frequency) being below the limit of detection by direct measurement. We have estimated this precursor frequency by titrating a known quantity of antigen-specific cells into naive recipients. Adoptive transfer of naive antigen-specific T cell receptor transgenic cells into syngeneic nontransgenic recipients, followed by stimulation with specific antigen, results in activation and expansion of both donor and endogenous antigen-specific cells in a dose-dependent manner. The precursor frequency is equal to the number of transferred cells when the transgenic and endogenous responses are of equal magnitude. Using this method we have estimated the precursor frequency of naive CD8 T cells specific for the H-2D(b)-restricted GP33-41 epitope of LCMV to be 1 in 2 x 10(5). Thus, in an uninfected mouse containing approximately 2-4 x 10(7) naive CD8 T cells we estimate there to be 100-200 epitope-specific cells. After LCMV infection these 100-200 GP33-specific naive CD8 T cells divide >14 times in 1 wk to reach a total of approximately 10(7) cells. Approximately 5% of these activated GP33-specific effector CD8 T cells survive to generate a memory pool consisting of approximately 5 x 10(5) cells. Thus, an acute LCMV infection results in a >1,000-fold increase in precursor frequency of D(b)GP33-specific CD8 T cells from 2 x 10(2) naive cells in uninfected mice to 5 x 10(5) memory cells in immunized mice.

Adoptive Transfer↗

PubMed2000

Scope and limitations of a new highly selective synthesis of unsymmetrical monomers for the synthesis of precursors toward poly(arylenevinylene)s

In our laboratory a precursor route to poly(p-phenylenevinylene) derivatives is developed in which unsymmetrically substituted p-xylene derivatives, possessing a benzylic sulfinylalkyl group, are used as monomers. Because of this unsymmetry, we were forced to investigate thoroughly the synthesis of these sulfoxides, as we start from symmetric and readily accessible molecules, namely, bis(halomethyl)-p-xylene derivatives. In a former publication, a new extremely effective route for the production of these unsymmetrically substituted sulfinyl monomers was presented. This paper expands upon these previously reported results. To examine the scope and limitations of this elegant route, this new method was applied to the synthesis of various derivatives not included in the initial work.

Journal Article↗

PubMed1983

The analysis of an anti-fluorescein cytotoxic response.

The detailed kinetics of the appearance of clones of anti-fluorescein cytotoxic T lymphocytes (CTL) in a primary limiting dilution response have been examined. The addition of factors from the supernatants of concanavalin A-stimulated rat spleen cell cultures was necessary to obtain linear dose-response curves and strong primary responses. In a standard primary response the maximum detectable number of specific clones was found, on day 5, to be derived from precursors having a frequency of 1 in 10 000 spleen cells. When limiting dilution cultures were restimulated on day 3, responses on day 5 were unaffected but new clones appeared on day 7 with a frequency of 1 in 1000. The emergence of the day-7 response depends on the addition of factor(s) on day 3. It is proposed that the early low frequency precursors detected on day 5 and the high frequency precursors detected on days 7-9 are derived from two stages in the differentiation lineage of CTL precursors. Restimulation of limiting dilution cultures involves not only the continued clonal expansion of primary responses but also the emergence of new "clones" of specific CTL.

Animals↗

PubMed1988

Limiting-dilution analysis of T cells extracted from solid human lung tissue: comparison of precursor frequencies for proliferative responses and lymphokine production between lung and blood T cells from individual donors.

This study evaluates the frequency and functions of immunocompetent T cells at the clonal level in solid human lung tissue versus peripheral blood. Enzymatic digestion of slices of histologically normal human lung yielded 18-42 x 10(6) viable mononuclear cells per gram wet weight tissue, of which 60-72% were lymphocytes; based upon these recoveries and the known weight of adult lung, the (median) lung parenchymal lymphocyte population can be estimated as 6 x 10(9), being of the same order as the blood pool and 15-30-fold that recoverable by broncho-alveolar lavage. Flow cytometric analysis indicated that the bulk of these lymphocytes was OKT3+/T11+ (CD3/CD2) T cells. Purified blood and lung T cells from each subject were cultured at limiting dilution in the presence of PHA, irradiated feeder cells and recombinant human IL-2. The mean frequency estimates for PHA-responsive T cells in these populations were 1 in 1.23 (81%) and 1 in 3.22 (31%) for blood and lung, respectively. This difference was seen for T cells from each donor and was highly significant by paired t-test (P less than 0.002). Analysis of surface phenotypes and functions of individual blood and T-cell clones indicated comparable frequencies for OKT4 (CD4) and OKT8 (CD8) expression, TNF production and mitogen-induced cytotoxicity. However, a striking inverse relationship was observed between the overall frequency of IL-2-producing clones (79% for blood versus 47% for lung) and interferon-gamma (IFN-gamma)-producing clones (46% versus 87%). These differences were found for each subject, and both were highly significant (P less than 0.001) by paired t-test. The available literature suggests that the majority of these lung T cells represent transient immigrants derived from the blood. Accordingly, the functional differences we have observed suggest either selective trapping within the lung vascular bed of peripheral blood T cells of certain functional phenotypes or alternatively selection/modulation of T cells by lung-derived factors during their transit through the tissue.

Adult↗