PHA Response Research Articles

Altered IL-10 levels in trauma patients' M� and T lymphocytes

Trauma results in concomitant immunosuppression and elevated monocyte (M phi) inflammatory cytokine levels. The augmenting or ameliorating effect of IL-10 in septic complications after trauma is controversial. Here, IL-10 levels of trauma patients' and normals' PBMC, isolated M phi, and isolated T cells were assessed and correlated to their PBMC mitogen responses, their T-cell proliferation in an APC independent system, and their M phi production of elevated TNF-alpha levels. Trauma patients with depressed PBMC responses to PHA stimulation also had significantly decreased IL-10 levels in their stimulated PBMC supernates (P = 0.0022) and their MDP-stimulated isolated M phi population (P = 0.0004). However, patients with depressed PHA responses could have either normal or depressed T-cell proliferation in an anti-CD3-, anti-CD4-stimulated system. If APC-independent T-cell proliferation was depressed, induced IL-10 levels were suppressed (P = 0.007). However, if APC-independent T-cell proliferation was normal or elevated, IL-10 levels could be normal or elevated (P = 0.018). Decreased IL-10 levels correlated with depressed mitogen responses and depressed T-cell proliferation. IL-10, therefore, could not be inducing trauma patients' immunosuppression. Patients with elevated M phi TNF-alpha levels had depressed M phi IL-10 levels.

Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis.

Experiments were designed to test the hypothesis that chronic exposure to tumor necrosis factor alpha (TNF) alters the function of activated T lymphocytes. Pretreatment of tetanus toxoid-specific T cell clones with TNF for up to 16 d impaired rechallenge proliferative responses to antigen in a dose- and time-dependent fashion. IL-2 and PHA responses were preserved. Prolonged treatment with TNF impaired production of IL-2, IL-10, IFN gamma, TNF, and lymphotoxin (LT) following stimulation with immobilized OKT3, and resulted in suboptimal expression of the IL-2R alpha chain (Tac) but not CD3, CD4, or HLA-DR antigens, when compared to untreated control cells. By contrast, pretreatment of T cells for prolonged periods in vitro with neutralizing anti-TNF monoclonal antibodies (mAb) enhanced proliferative responses, increased lymphokine production, and upregulated Tac expression following stimulation with OKT3. To determine whether TNF exerts immunosuppressive effects on T cells in vivo, we studied cell-mediated immunity in patients with active rheumatoid arthritis (RA), before and after treatment with a chimeric anti-TNF mAb. Treatment with anti-TNF restored the diminished proliferative responses of PBMC to mitogens and recall antigens towards normal in all patients tested. These data demonstrate that persistent expression of TNF in vitro and in vivo impairs cell-mediated immune responses.

Effect of met-enkephalin on the proliferative response of equine peripheral blood mononuclear cells and purified T lymphocytes

Summary Enkephalins (ENK) are synthesized by neurons, glia, diverse carcinomas and various cells of the immune system. Work in other species indicates that exercise affects plasma concentrations of ENK. Various studies suggest that this may result in altered resis- tance to disease and progression of existing diseases. The present study was performed in order to determine whether Met-ENK may regulate the proliferative response of equine peripheral blood mononuclear cells (PBMCs) or isolated T cells. Quadruplicate aliquots of PBMCs from two geldings (G), T cells from one gelding (G) and PBMCs from one adult mare (M) were incubated with suboptimal concentrations of the T cell mitogen phytohemaggluti- nin (PHA), in the presence or absence of 10s, 107, 10-9 and 1011 M Met-ENK. Treatments were added at the beginning of culture and the incorporation of 3H-thymidine was measured on day 3. The l o-s M ENK treatment inhibited mitogen-induced proliferation of PBMCs from G whereas the PHA response of G PBMCs was stimulated by 10 -11 M ENK treatments. For cells collected from M, PHA-blastogenesis was significantly reduced by 10 -5 , 10 -9 and 10 -11 M ENK treatments. There was no stimulatory effect of ENK on PHA-responsiveness of PBMCs from M. The PHA-stimulated response of T cells was enhanced by 10 -7 and 10 -9 M ENK treatments. Lower and higher ENK concentrations had no effect on the proliferation of T cells. Results from this experiment suggest that physiological to superphysiological concentrations of ENK may effect the non-specific proliferative response of equine im- mune cells. Whether endogenous enkephalins act to modify the resistance of horses to various infectious diseases requires further study. Veterinary Medicine, Baton Rouge, LA 70803.

The effect of aspirin on mononuclear cells in aspirin-sensitive asthmatics and control subjects.

Three groups, comprising normal subjects (n = 10), aspirin-sensitive asthmatics (ASA+; n = 10) and aspirin-insensitive asthmatics (ASA-; n = 10) were entered into a blinded, parallel group study to asses the modulating effect of aspirin (ASA; 0.0275, 0.275, 1.385, 2.75, 6.9, 13.8 and 27.5 microM) on lymphocyte proliferation in vitro, either alone or in combination with the mitogen, phytohemagglutinin (PHA; 10, 25, 50, 100, 200 and 500 micrograms/ml). The percentage and absolute numbers of CD4-positive T cells (normals: 51.3%; ASA+: 51.1%; ASA-: 46.1%; p = 0.4038) and CD8-positive T cells (normal: 27.5%; ASA+: 26.4%; ASA-: 28.4%; p = 0.8408) did not differ significantly between the groups. Significant differences in mean PHA responses between ASA+, ASA- and normal subjects were observed when peripheral blood lymphocytes (PBL) were exposed to PHA concentrations over the range 10-50 micrograms/ml; PHA 10 micrograms/ml (p < 0.005), PHA 25 micrograms/ml (p < 0.005) and PHA 50 micrograms/ml (p < 0.01), the lowest and highest proliferative responses being obtained with PBL from ASA+ and ASA-, respectively. However, at higher PHA concentrations (100-500 micrograms/ml), differences between the three groups were not observed. When ASA was added in combination with PHA, augmentation of the PHA response was observed with cells from all three groups but was most marked in the ASA+ group, especially at lower PHA concentrations (10-50 micrograms/ml) in combination with 0.275-13.8 microM ASA.(ABSTRACT TRUNCATED AT 250 WORDS)

Defective T‐cell stimulatory pathways in patients after allogeneic bone marrow transplantation (BMT) in man

Immunological reconstitution after allogeneic bone marrow transplantation in man is characterized by a decreased lymphocyte transformation response to various mitogens and antigens during a period of from months to years. One reason for the decreased proliferative capability could be an inverted CD4/CD8 ratio; however, the present investigation demonstrates that this is not the only explanation for the immunodeficiency, since the CD4 as well as the CD8 subset, when studied in isolation, have qualitative defects, as evidenced by a reduced response of both subsets to stimulation with PHA, anti-CD2 and anti-CD3 MABs. The reason for the qualitative defect is unknown but a distorted composition of the CD4+ as well as the CD8+ T-cell subsets is suggested by the present investigations. We also observed that the PHA response was almost completely reconstituted one year after BMT, while the PWM response was still severely affected. The present study suggests that T-cell subsets which differ in their capacity to respond to PHA and PWM have different kinetics of reconstitution after BMT.

Using serial observations to identify predictors of progression to aids in the Toronto Sexual Contact Study

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrolment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989,41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrolment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrolment were significantly associated with elevated risk. In order to evaluate the impact of the serial observations of immune function variables, these variables were lagged one year in a model with other time dependent covariates; the following point estimates of relative risk of progression to AIDS were observed: for a unit decline in T4/T8 ratio, RR = 60.8 ( p < 0.0001); for a 10,000 cpm decline in PHA response, RR = 1.09, ( p = 0.07); for a 100 μg/l increase in IgA, RR = 1.33, ( p = 0.02); for the development of oral hairy leukoplakia, thrush, or herpes zoster, RR = 2.69, ( p = 0.02); and treatment with zidovudine, RR = 0.06, ( p = 0.01).

Lymphocyte Subpopulation Number and Function inInfancy

Normal values for percentages of lymphocyte subpopulations and functional responses to mitogen stimulation in infancy are not well established. In the present study, lymphocyte subpopulations were examined in umbilical cord blood samples and in peripheral blood samples drawn before 7 and 24 months of age (mean age 10.4 months) from a healthy population of infants born in Tucson, Arizona. Results indicate significant increases occurred from birth to later infancy in the percentages of total T cells (CD3), T-cell subsets (CD4, CD8) and B cells (CD20). The CD4/CD8 ratio and the functional responses to ConA and PWM mitogens significantly decreased from birth to later infancy. PHA responsiveness did not show a significant change. Results from cross-sectional analyses (n=271) were supported in a smaller longitudinal subset (n=37). There were no detectable ethnic- or gender-related differences in cord blood or samples obtained in later infancy. The normal values established in this study will be useful in studies of immune-system maturation and in the clinical evaluation of newborns, infants, and toddlers suspected of either acquired or congenital immune-deficiency states.

The effect of aging on cell-cycle kinetics and X-ray-induced chromosome aberrations in cultured lymphocytes from patients with Down syndrome.

To evaluate the effects of aging on cytogenetic characteristics of lymphocytes from Down syndrome (DS), cell-cycle kinetics after PHA stimulation and chromosome-type aberration frequencies after X-ray exposure were investigated in vitro in the lymphocytes derived from 4 (or 3 for X-ray treatment) age groups of DS patients and age-matched controls. The results clearly showed higher mitotic and proliferation index levels in younger groups compared to older groups at the various culture intervals, whether the lymphocytes were from the DS patients or controls. The age-related changes of the proliferation index were mainly attributed to a delayed response to PHA as age increased. The changes of PHA responses seemed to be particularly marked during adolescence. Nonetheless, no significant differences were observed between the DS patients and age-matched controls for each age group. In all age groups, frequencies of both chromosome-type exchanges and deletions were elevated in the DS patients by about 1.3 times in comparison with the controls. The magnitude of radiosensitivity, however, seemed to decrease slightly in the 40-49-year group. To our knowledge, the present study is the first report in the literature to deal with the effect of aging on the greater radiosensitivity of DS lymphocytes.

Inhibition of interleukin-2 production and lymphocyte responsiveness by the cell activation inhibitor, CI-959

CI-959 (5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-yl-benzo [b]-thiophene-2-carboxamide), an antiallergy compound, blocked release of IL-2 from Con A stimulated rat splenocytes and human lymphocytes with respective IC50s of 19.1 and 23.1 microM. Inhibition of IL-2 production required the presence of CI-959 in culture medium for the first 9 hr. CI-959 also inhibited Con A-stimulated rat and human lymphocyte proliferation with IC50s of 4.7 and 5.4 microM, respectively. Inhibition of the Con A proliferative response could not be overcome by exogenous recombinant human IL-2 (300 units/ml) in either the rat or human systems. Although potent in the human mixed lymphocyte reaction (IC50 = 3.5 microM), CI-959 was less effective in blocking the PHA response (IC50 = 43.9 microM), and had minimal effect on the release of IL-1 and TNF alpha from LPS-stimulated human monocytes. These findings suggest that CI-959 selectively inhibits some lymphocyte functions, as opposed to monocyte functions, and that among these is the production of IL-2.

T-lymphocyte response to cytokines in B-chronic lymphocytic leukemia

The mechanisms underlying abnormal T-cell function in B-chronic lymphocytic leukemia (B-CLL) are unknown. We have studied B-CLL T-cell activation pathways in the rigorous absence of leukemic cells and with controlled numbers of accessory cells present. The responsiveness to added recombinant IL-1 and IL-2 was assessed. We have found that under optimal culture conditions B-CLL T cells had a normal PHA-induced proliferative response in terms of incorporated 3H-thymidine per T cell. Also the capacity of mitomycin-C treated B-CLL monocytes to support autologous T-cell mitogenesis was normal. However, a subtle difference between normal and B-CLL T cells emerged with respect to cytokine responsiveness. While the PHA response of purified normal T cells in the absence of monocytes was augmented by rIL-1, this could not be demonstrated for B-CLL T cells. A much greater degree of augmentation occurred with added rIL-2 in the case of both normal and B-CLL T cells. In the presence of 20% autologous monocytes rIL-1 and rIL-2 had no effect on mitogenesis. We conclude that B-CLL T cells have an abnormal profile of cytokine responsiveness which is consistent with observed abnormalities of subset distribution, and which may contribute to the clinical immunodeficiency in B-CLL.

Is Phaseolus vulgaris Leucoagglutinin (PHA‐L) a Useful Markerfor Labeling Neural Grafts?

The lectin Phaseolus vulgaris leucoagglutinin (PHA-L) has come into wide use as an anterograde neuroanatomical tracer. The ability of this lectin to fill entire neurons and remain in place over long periods suggested it might be an ideal marker for donor cells to be grafted into hosts for long survival periods. We have used the lectin PHA-L to mark fetal rat olfactory bulb (OB) cells prior to grafting into host rat OBs. Hosts were sacrificed at various times up to 9 weeks after grafting, and tissue was immunohistochemically processed for PHA reactivity. After 2 and 4 weeks survival, sparse patterns of labeled cells were observed within the host OBs. However, after 9 weeks survival, few if any labeled cells were visible within host tissue. We conclude that PHA-L may be a less than satisfactory marker for fetal rat cells (other than astrocytes) which are to be identified in host tissue after a period of several weeks.

Are soluble monocyte-derived HLA class II molecules candidates for immunosuppressive activity?

Supernatants of human blood monocyte cultures suppressed PHA responses (IL-2 synthesis, IL-2R expression, DNA synthesis) of autologous and allogeneic lymphocytes. The main suppressive activity was found in the 65-kDa (and 23-kDa) range. It could be incompletely neutralized by mAb specific for a non-polymorphic HLA DR determinant and could also be adsorbed to and eluted from an anti-DR immunoabsorbent column. On blots of monocyte lysates and monocyte culture supernatants, the mAb RoDR recognized antigens of nearly the same M r. The hypothesis that soluble HLA DR αβ heterodimers or β chains are likely candidates for the suppressor factor was confirmed by analogous effects of purified HLA DR molecules. We favor a model in which soluble MHC class II molecules (in contrast to surface-bound ones) may interfere with the association and cross-linking processes necessary for T cell activation by competing for CD4 binding sites.

Effects of recombinant human erythropoietin on HLA sensitization and cell mediated immunity

Highly presensitized patients wait longer for a renal allograft than unsensitized patients and have a poorer allograft survival rate. Repeated blood transfusions have been implicated in the induction and maintenance of sensitization. To determine the effect of recombinant human erythropoietin (rHuEPO) therapy on five transfusion dependent, highly sensitized adolescents on dialysis, we serially measured percentage panel reactive antibody (%PRA) levels, titers of identifiable discrete anti-HLA Class I antibody specificities, and non-specific indices of cellular immunity before and following initiation of rHuEPO therapy. Although four of the five patients had previously rejected at least one renal allograft, the removal of chronic antigenic stimulation from blood transfusions led to a marked reduction in anti-HLA antibody titers to recognizable private and public specificities (P less than 0.001) and a reduction of mean %PRA from 80% to 56% (P less than 0.05). Each patient demonstrated a reduction of two or more dilutions to at least two anti-HLA antibody specificities. A control group of five patients matched for age, transfusion dependence and sensitization status demonstrated no change during a comparable time interval. PHA responsiveness decreased significantly in the rHuEPO group whereas autologous and allogenic mixed lymphocyte response, spontaneous blastogenesis and T-cell subsets did not. These data indicate that in highly sensitized dialysis patients rHuEPO may lead to decreased sensitization, shorter waiting time on dialysis and possibly improved allograft survival rates.

HISTOCHERICAL CHARACTERIZATION OF PHA BINDING SITES IN CULTORED COEEIAC KUCOSA

Qualitative changes in lectin binding characteristics in coeliac disease have been previously described (Histochemistry 88,105,1988); in particular, the expression of PMA binding (Gal-GalMac residues) in goblet cells of coeliac mucosa appears to be an important point of histochemical difference between coeliac and control mucosae. In order to verify whether this PHA reactivity is modified in culture system, with and without the addition of a peptic-tryplic digest of A-gliadin (PI) at a concentration of 0.1 mg/ml, we have studied 4 cases of untreated coeliac mucosae placed in culture for 30 h in a serum-containing medium. All Bovin's solution-fixed paraffin-embedded sections were incubated with PHA-NRP conjugated lectin (Sigma Chemical Co.) as extensively elsewhere reported (Histochemistry 88, 105, 1988); prior to staining with PHA, parallel sections were digested with neuraminidase from Vibrio Cholerae (Calbiochem Corp.)(Lab Invest 47, 383, 1982). Adequate control procedures were also carried out. Flat intestinal mucosa from all coeliac patients underwent a clear morphological improvement when cultured for 30 h in the absence of PI and enterocyte height was considerably increased after culture. When the tissue culture was performed in the presence of PI, mo morphological or morphometric improvement was observed and necrotic areas and cell debris were found. An evident PNA reactivity was observed in the supranuclear region of enterocytes of regenerating mucosae and also in samples treated with PT;this PNA reactive pattern is unmodified by neuraminidase pretreatment. Inflammatory cells in the lamina propria are greatly stained after neuraminidase digestion. In uncultured samples of duodeno-jejunal biopsies from same patients, only goblet cells were reactive. Therefore we contend that untreated coeliac mucosae in culture system express new PHA binding sites as a consequence of quantitative changes in glycoproteins synthesis and secretion, as previously reported(6Ut 30,1339, 1989);t he unmodified PHA pattern after neuraminidase digestion may suggest an altered glycosilation in enterocytes since sialic acid groups are not incorporated or lacking in oligosaccharide chains.

Immunopharmacological properties of a protein-bound histamine metabolite

Histamine metabolite was prepared by incubating histamine dihydrochloride and diamino oxidase for 24 h at 37°C. Radioactive histamine was used for monitoring the whole procedure and to select the best experimental protocol. Pharmacological activities of histamine are abolished by this procedure. Histamine metabolite was found to bind to the serum proteins, to inhibit the PHA response of mouse and human mononuclear cells and to accelerate mortality rates in tumor-bearing mice. Thin layer chromatography allowed separation of metabolite from histamine and from known imidazol-derived compounds. This is the first experimental evidence for immunological properties ascribed to a histamine metabolite.

Interleukin 2 receptor expression by T cells in human aging

Aged individuals have depressed cell-mediated immunity and diminished T cell proliferation to mitogenic and antigenic stimuli. Because T cell responses depend on the surface expression and normal function of interleukin 2 receptors, we measured the quantities and affinities of cell surface IL-2R and the amount of soluble IL-2R α chain (p55) release in vitro in PHA-stimulated mononuclear cells from healthy aged (⩾65 years old) and young (⩽39 years old) donors. At the peak of the PHA response, the fraction of cells expressing IL-2R α chain (CD25+) was lower in the aged (43% vs 56%, P = 0.033). Relative to the lower proliferation and CD25 expression, old donor cells released unexpectedly high quantities of soluble α chain into culture supernatants. However, the average affinities and the mean numbers of high- and low-affinity surface receptors per CD25+ cell were equivalent in cells from eight pairs of aged and young donors (1850 vs 1586 high affinity, and 20,655 vs 23,466 low affinity, P > 0.2 for both). The soluble IL-2R released by stimulated cells had no effect on proliferative responses, because addition of saturating doses of exogenous recombinant IL-2 did not increase cellular proliferation, and addition of soluble anchor-minus recombinant IL-2R α chain did not suppress it. These results indicate that in healthy older individuals, diminished numbers of T cells can be induced to express cell surface IL-2R following mitogenic stimulation, although aged CD25+ cells express a normal complement of IL-2R molecules. In the aged, either CD25+ cells release excessive quantities or a subset of cells synthesizes and releases soluble IL-2R α chain into the extracellular environment without expressing it on the cell surface.

LETHAL GRAFT-VERSUS-HOST REACTION AGAINST NON-H-2 ANTIGENS

Injection of B10.D2 cells into irradiated H-2d compatible (DBA/2xB10.D2)F1 recipients provokes a lethal GVH that can be abrogated by donor preimmunization against host-specific DBA/2 non-H-2 antigens. To study the possible relationship between the observed protection and restoration of immune responsiveness, we compared spleen cellularity, selected T and B cell functions, and NK activity in GVH and protected mice during the 1st month after grafting. Normal and isografted mice served as controls. GVH was found to be characterized by an early stimulation phase associated with splenomegaly and increased percentages (but not numbers) of Lyt-2+ and L3T4+ cells, followed by profound aplasia and abrogation of IL-2 production. Response to a B cell mitogen (LPS) is depressed, and cells from GVH mice exert a strong suppressive effect on the LPS and PHA responsiveness of normal cells. Suppression appears to be mediated by a radioresistant, nylon nonadherent, asialo GM1 negative cell expressing a low level of Thy-1 antigen. In contrast, protection correlates with progressive restoration of spleen cellularity and LPS responsiveness, with decreased but clearly detectable IL-2 production, and transient nonspecific suppressor activity. The immune status of protected mice resembles that of isografted controls. No correlation was found between mortality (or protection) and either PHA responsiveness, which remained depressed in all grafted mice throughout the observation period, or NK activity, which was strongly depressed in both GVH and protected mice. In conclusion, protection correlates with the disappearance of nonspecific suppressor cells and the restoration of cellularity and certain nonspecific immune functions. Donor immunization against host-specific non-H-2 antigens, which protects against mortality, also protects against GVH-associated immune deficiency.

Influence of early rearing on lymphocyte proliferation responses in juvenile rhesus monkeys

Lymphocyte proliferation responses and natural killer cell activity were evaluated in 35 juvenile rhesus monkeys derived from five different rearing conditions. Nursery-reared monkeys had proliferation responses which were significantly higher than those of mother-reared subjects. Reexamination of the nursery-reared monkeys 1.5 years later indicated that an abnormally high response to concanavalin A was still evident at 2.5 years of age, but both PHA and PWM responses had shown an age-appropriate decrease into the normal range for this species. Proliferation responses in monkeys that had been weaned early from their mothers at 6 months of age were also higher than values for control monkeys that remained with their mothers, but below those of the nursery-reared monkeys. In contrast, monkeys that had received multiple separations from the mother between 3 and 7 months of age showed lymphocyte proliferation responses that were below normal. These results indicate that early rearing conditions can have a lasting effect on certain immune responses in the developing primate.

EFFECT OF A NEW IMMUNOSUPPRESSIVE AGENT, FK506, ON HUMAN LYMPHOCYTE RESPONSES IN VITRO

The effect of FK506 on in vitro human lymphocyte responses was assessed in comparison with cyclosporine. FK506 suppressed, in a dose-dependent fashion, the lymphocyte response to stimulation with PHA and with alloantigens in primary mixed lymphocyte reactions at a 70-100-fold lower concentration than CsA--namely, 50% inhibition (IC50) was obtained with 8.6 nM FK506 and with 750 nM CsA in the PHA response, and with 0.21 nM FK506 and with 20 nM CsA in MLR. Allocytolytic T lymphocyte induction was also inhibited by FK506, whereas the ability of CTL to lyse targets was not affected by the agent, indicating that FK506 did not affect the recognition and binding of alloantigen by CTL. FK506 inhibited, in a dose-dependent fashion, both IL-2 receptor and transferrin receptor expression on the alloactivated lymphocytes--whereas this agent inhibited only incompletely both expression of both receptors on lymphocytes stimulated with PHA. Lymphocytes from primary MLR cultured in the presence of FK506 were tested for suppressor cell activity on day 8 of culture. FK506 did not allow for the expression of alloantigen-activated suppressor cells when used in a dose sufficient to inhibit CTL generation.

Modulation of Immunological Abnormalities of Growth Hormone‐Deficient Children by Growth Hormone Treatment

We studied the immunomodulatory role of growth hormone (GH) treatment in GH-deficient children. GH potentiated natural killer (NK)-cell activity and the PHA and Con-A lymphocytoproliferative response. Two-color fluorescence using monoclonal antibodies (CD4, 2H4, CD8 and CD11) showed a moderate reduction of the helper T cells and NK cells, but no changes of suppressor T cells or cytotoxic T-cells during GH therapy. Cancer and slow viral infection in GH-deficient children have been watched for carefully before and after GH therapy.