Lymphocyte Interleukin-2 Research Articles

Lymphokine Activated Killer Cells Enhance IL-2 Prevention of Sepsis-Related Death in a Murine Model of Thermal Injury

It has previously been shown by this laboratory that immunomodulation of thermally injured animals with low-dose interleukin-2 (IL-2) and indomethacin (Indo) improves survival following septic challenge. Lymphokine-activated killer (LAK) cells have been shown to be effective in certain viral infections and to act in synergy with IL-2 in the treatment of certain types of cancer. We have studied the effect of LAK cells in combination with IL-2 and Indo in a murine model of thermal injury and sepsis. Male A/J mice received a 25% scald burn injury or sham burn and were randomized into five groups: (a) sham/vehicle, (b) burn/vehicle, (c) burn/IL-2 (250 U) + Indo (5 μg), (d) burn/LAK cells (2 × 106 cells), or (e) burn/LAK cells + IL-2 + Indo and were treated accordingly for 6 days following injury. LAK cells were generated by in vitro IL-2 treatment of syngeneic spleen cells for 72 hr and cytotoxic activity was confirmed by standard 51Cr release assay using natural killer (NK)-sensitive and NK-resistant targets. In the groups receiving LAK cells they were administered on Day 1 and Day 6 postinjury. On Day 10, septic challenge by cecal ligation and puncture (CLP) or splenectomy, for in vitro studies, was performed. Five-day survival after CLP was 80% in the sham/vehicle group compared to 0% in the burn/vehicle group (P < 0.01). IL-2/Indo and LAK/IL-2/Indo improved survival to 25% (P < 0.05) and 57.1% (P < 0.01), respectively. In vitro lymphocyte IL-2 production in response to mitogens was increased in the LAK/IL-2/Indo group compared with the burn/vehicle group (3 U/ml vs 2 U/ml, respectively, P < 0.05). IL-2/Indo alone had no significant effect on these in vitro parameters. As shown previously, monokine (IL-1, IL-6, and TNF) secretion by adherent splenocytes in response to LPS was markedly increased following thermal injury; no change was observed with any of the therapeutic protocols. We conclude that combined LAK/IL-2/Indo therapy is an effective regime for reduction of sepsis-related mortality and that LAK cells act synergistically with IL-2 to improve in vitro parameters of immune function in this model.

Autoimmunity in schizophrenia: a review of recent findings.

The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.

The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1.

The gene encoding the gamma chain of the lymphocyte interleukin-2 receptor has been cloned and shown to be required to associate with the beta chain in order for IL-2 internalization and cell activation to occur (1). We considered this gene, IL2RG, a candidate for the X-linked form of severe combined immunodeficiency at the SCIDX1 locus, in which affected males have impaired lymphocyte development. Using fluorescence in situ hybridization and PCR amplification of somatic cell hybrid DNAs, we mapped IL2RG to human Xq13.1, a location within the SCIDX1 critical region established by linkage analysis. The 4.2 kb IL2RG gene was sequenced, and its genomic organization was elucidated. Seven of 19 transformed B-lymphocyte cell lines with independent SCIDX1 mutations had absent or minimal IL2RG mRNA. Unique point mutations were documented to be specifically associated with the disease and the carrier state in four unrelated affected males and their family members: one in a boy with no detectable IL2RG mRNA, in which the mutation ablated a splice donor site; one causing premature chain termination; and two causing distinct amino acid changes. The demonstration of impaired IL2RG mRNA expression in males with X-linked SCID and of unique point mutations in SCIDX1 pedigrees constitutes powerful evidence that the SCIDX1 gene is IL2RG. Noguchi et al. (2) have independently published IL2RG mapping to Xq13 and discovery of mutations in three affected males. The specific pathogenesis of IL2RG mutations and approaches to gene therapy can now be addressed in the X-linked form of SCID.

Reversal of immune dysfunction in osteopetrotic rats by interferon-γ: Augmentation of macrophage Ia expression and lymphocyte interleukin-2 production and proliferation

Lymphocytes from osteopetrotic (op) rats, compared to their normal (n) littermates, exhibit defective immune functions associated with their inability to resorb bone. Among these immune defects are the failure of their spleen cells to proliferate normally to mitogens and to generate IL-2. Addition of exogenous IL-2 failed to reverse the suppressed proliferation in the op spleen cells, indicating that additional defects were involved in the suppression. Phenotypic analysis of cellular constituents of op and n spleens revealed that the percentages of T cells, macrophages, and IL-2 receptor positive cells were not different. Furthermore, there was no difference in CD4 ( W3 25 ) and CD8 (OX8) cells. However, the Ia + (OX3) cells in the op spleen represented <50% of those found in the n spleen, but the op had higher levels of transferrin receptor (OX26). On the basis of the ability of interferon-γ (IFN-γ) to increase Ia expression, this cytokine was added to op spleen cells (10–50 U/ml) and found to increase the number of Ia + cells to the level found in n spleen cells. Moreover, pretreatment of op spleen cells with IFN-γ restored their ability to proliferate to mitogens and their responsiveness to IL-2. Not only did IFN-γ reverse the defective response to IL-2, but it also augmented the defective IL-2 production by op spleen cells. Taken together, these findings demonstrate that IFN-γ can reverse many of the impaired immune functions characteristic of op spleen cells in vitro. Furthermore, these data suggest that IFN-γ may provide an important avenue of treatment in these animals that may contribute to restoration of normal bone resorption.

Dietary Arginine Supplementation Does Not Enhance Lymphocyte Proliferation or Interleukin-2 Production in Young and Aged Rats

Recent studies indicate that supplemental arginine may enhance in vitro lymphocyte mitogenesis. To determine whether dietary arginine could reverse age-associated losses in immune functions, we fed purified amino acid diets to young (2-mo-old) and aged (24-mo-old) Fischer 344 rats. Rats receiving control (1.12% arginine) or supplemented (3% arginine) diets were pair fed to intakes of deficient (0% arginine) rats. Another group was fed the supplemented diet ad libitum. On d 15, responses of splenocytes to phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were lower (P less than 0.01), but interleukin-2 (IL-2) production was higher (P less than 0.05) in aged rats than in young rats. At mitogen doses producing maximal stimulation, supplemental arginine did not enhance PHA-, Con A- or PWM-stimulated lymphocyte proliferation; PWM responses at sub-maximal doses were higher in pair-fed supplemented rats than in control or ad libitum supplemented rats (P less than 0.05). Arginine supplements did not increase thymus weights or IL-2 production above controls. In another experiment, weanling rats received control and supplemented diets in amounts equal to the intake of deficient rats for an average of 37 d. Splenocytes were cultured with mitogens at various arginine levels. No diet effect was observed. Mitogenesis was maximal when media arginine approximated normal plasma levels. Our results suggest that supplemental arginine has little effect on lymphocyte proliferation or IL-2 production in healthy young and aged rats.

Deficiency in the incorporation of labeled thymidine and inhibition in the biosynthesis of interleukin-2 in lymphocytes obtained from Histoplasma capsulatum infected mice

The incorporation of (3H) thymidine and the biosynthesis of interleukin-2(IL-2) were investigated in Concanavalin A (ConA) and histoplasmin stimulated lymphocytes from spleen of infected Balb/c mice with the yeast phases of Histoplasma capsulatum. The ability to incorporate (3H) thymidine of Con A stimulated lymphocytes in culture from spleen of Histoplasma capsulatum infected mice, as well as the IL-2 content present in the supernatants of that cultures, were depressed along the first three weeks of the experiments, but starting week five, normal values were restored or even discretly increased. Incorporation of (3H) thymidine in histoplasmin stimulated lymphocytes remained inhibited along the seven weeks the experiment lasted. Results showed that inoculation of H. capsulatum yeast in mice provoked a temporary immunosuppression on cell mediated immunity, that can be explained by means of the inability of T cells to produce enough IL-2 necessary for the proliferation of T cells in culture.

Thymosin α 1 potentiates interleukin 2-induced cytotoxic activity in mice

We have investigated the effects of interleukin 2 (IL-2) on cytotoxic activity of spleen lymphocytes, from normal and cyclophosphamide (200 mg/kg) or B-16 melanoma suppressed mice, after in vitro or in vivo pretreatment with thymosin α 1 (TA1). The results of this study indicate that pretreatment in vitro (100 ng/ml for 1 hr) or in vivo (200 μg/kg/day for 4 days) with thymosin α 1 (TA1), significantly increased the IL-2 (from 100 to 500 U/ml) in vitro induced cytotoxic activity of spleen lymphocytes, collected from both normal and cyclophosphamide and tumor-suppressed animals, against both YAC-1 (NK sensitive) and MBL-2 (NK resistant) cell lines. The potential use in combination of these two different biological response modifiers, useful in enhancing the immunological responses to IL-2 of lymphocytes, may provide a novel model of immunotherapeutic intervention in cancer.

Selective enhancement of synthesis of interleukin-2 in lymphocytes in the presence of ciprofloxacin

A study was performed to verify the effect of ciprofloxacin on the production of interleukin-2 and other cytokines in cultures of human peripheral lymphocytes. In the presence of ciprofloxacin, lymphocytes demonstrated increased synthesis of interleukin-2 (100-fold, 7-fold and 1.5-fold increase at ciprofloxacin concentrations of 80, 20 and 5 micrograms/ml respectively), as measured by radioimmunoassay. Synthesis of other cytokines from T lymphocytes, gamma-interferon, lymphotoxin and granulocyte-macrophage colony stimulating factor as well as interleukin-1 and tumour necrosis factor from monocytes was not increased, but inhibited at a ciprofloxacin concentration of 80 micrograms/ml. Thus the effect of ciprofloxacin resulting in enhanced synthesis of interleukin-2 seems to be specific.

Inhibition of lymphocyte blastogenesis caused by suppression of interleukin-2 receptor sites after thermal injury.

Burn patients often exhibit prolonged cell-mediated immune suppression. Of the mechanisms proposed to account for this, one invokes an inability on the part of T lymphocytes to undergo blastogenesis, clonal expansion, and differentiation--a process partially mediated by interleukin-2. Triplicate samples of 10% dilutions of burn serum from nine burn patients (three with greater than 60% burn) were analyzed for their ability to suppress mitogen-induced lymphocyte blastogenesis. A separate aliquot of stimulated cultured lymphocytes was tagged with a monoclonal antibody to interleukin-2 receptors. The serum of patients with greater than 60% burn was significantly more suppressive (as measured by depressed tritiated thymidine incorporation by cultured lymphocytes) than that taken from patients with smaller burns. In addition, serum from those with larger burns caused a marked reduction in the interleukin-2 receptor-labeling index, suggesting that it possesses factor(s) that directly or indirectly block T lymphocyte interleukin-2 receptor expression.

Cyclic AMP--an intracellular second messenger for interleukin 1.

We demonstrated that interleukin 1 (IL-1), a potent peptide mediator in immune and inflammatory responses, stimulates the synthesis of cAMP in a variety of IL-1-responsive cell targets. We also showed that cAMP analogs and cAMP-inducing agents can replace IL-1 in the induction of interleukin 2 receptors on lymphocytes as well as in phytohemagglutinin-induced murine thymocyte proliferation. By use of IL-1 and the cAMP-inducer, forskolin, a direct correlation between the induced level of cAMP and the degree of lymphocyte interleukin 2 receptor expression or thymocyte proliferation was established. Our results indicate that cAMP may be an important intracellular second messenger for IL-1.

T-cell functional defects in rheumatoid arthritis: Intrinsic or extrinsic?

This study investigated two mechanisms which may underlie abnormal T-cell function [lymphocyte proliferation and interleukin-2 (IL-2) production] in rheumatoid arthritis (RA). These were: (a) a possible lack of the IL-2-producing CD4 +2H4 + lymphocytes and (b) the possible inhibitory role of monocytes and neutrophils. Numbers of CD4 +2H4 + cells did not differ between normal controls and patients with RA, although IL-2 produced by the peripheral blood mononuclear cells (PBMC) of the same individuals was markedly reduced in the patient group ( P < 0.001). Many rheumatoid peripheral blood mononuclear cell preparations, but very few control, were contaminated with neutrophils ( P < 0.001). This was more marked in patients with active RA than in those with inactive disease ( P < 0.001). Numbers of monocytes were similar in all groups. Monocyte depletion, or addition of indomethacin and/or catalase in PBMC, caused a significantly greater increase of responses in RA patients than in controls. This effect was significantly higher in patients with active disease than in the inactive group. These findings suggest that activated monocytes and neutrophils found in the rheumatoid PBMC preparations exert inhibitory effects mediated, in part, by the production of prostaglandins and reactive oxygen intermediates. Monocyte depletion and partial reconstitution resulted in significant increase of lymphocyte proliferation and IL-2 production in both controls and patients. None of the manipulations performed succeeded in normalizing the deficient rheumatoid T-cell responses. These data support the hypothesis that non-lymphoid cell populations play an important role in the T-cell dysfunction characteristic of RA. This may explain the differences in the functional capacity of lymphocytes observed between cells derived from different sites or different stages of the disease.

Evidence that 8-methoxypsoralen (8-MOP) is a T-lymphocyte immunomodulatory agent

This study was designed to characterize the effects of the anti-psoraiatic compound 8-methoxypsoralen (8-MOP) on human lymphocyte function in vitro. Normal human peripheral blood mononuclear cells were stimulated with an optimal (1%) or a suboptimal (0.05%) concentration of phytohemagglutinin (PHA). At the optimal concentration of PHA, 8-MOP (140 μM) caused a delay in lymphocyte proliferation, interleukin-2 (IL-2) production/accumulation and IL-2 receptor expression. Addition of exogenous IL-2 to cultures stimulated with an optimal concentration of PHA did not overcome the delay of lymphocyte proliferation and IL-2 receptor expression. At the suboptimal concentration of PHA, 8-MOP (140 μM) caused a sustained inhibition of lymphocyte proliferation, IL-2 production/ accumulation and IL-2 receptor expression. Addition of exogenous IL-2 under these conditions restored the magnitude of lymphocyte proliferation and IL-2 receptor expression. However, the responses displayed the delayed lymphocyte proliferation and IL-2 receptor expression typical of cells incubated with 8-MOP and an optimal concentration of PHA.

Differential reconstitution of azidothymidine-induced inhibition of mitogenic responses by interleukin-2 in lymphocytes from patients with the acquired immunodeficiency syndrome : Nokta, M. and Pollard, R.B., University of Texas Medical Branch, Galveston, TX, U.S.A.

Differential reconstitution of azidothymidine-induced inhibition of mitogenic responses by interleukin-2 in lymphocytes from patients with the acquired immunodeficiency syndrome : Nokta, M. and Pollard, R.B., University of Texas Medical Branch, Galveston, TX, U.S.A.

Influence of sodium diethyldithiocarbamate (Imuthiol ®) on lymphocyte function and growth in weanling pigs

Mitogen-stimulated lymphocyte proliferation, delayed-type hypersensitivity (DTH) reactions, interleukin-2 (IL-2) production, and growth performance were evaluated in 3-week-old pigs treated with imuthiol. Lymphocyte proliferative responses to Con A and PWM were reduced ( P < 0.05) in pigs treated with imuthiol at 25 mg/kg; PHA proliferative responses were not influenced by imuthiol treatment. Imuthiol at 2.5 mg/kg and 25 mg/kg lowered IL-2 production when compared to saline-treated controls. Delayed-type hypersensitivity responses to PHA were higher in 25 mg/kg imuthiol-treated pigs; however, 2.5 mg/kg imuthiol-treated pigs had lower DHT reactions. Imuthiol at 2.5 mg/kg and 25 mg/kg reduced ( P < 0.05) average daily feed intake. These data suggest that in vivo imuthiol treatment in pigs lowers lymphocyte proliferative responses, IL-2 production, and growth performance.

Beta-adrenergic-receptor-mediated suppression of interleukin 2 receptors in human lymphocytes.

Adrenergic receptor agonists are known to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of beta-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the beta-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of beta-adrenergic agonists on expression of the high affinity IL-2 receptors, [125I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of beta-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that beta-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites.

Lymphocyte Interleukin 2 Production and Responsiveness Are Altered in Patients With Primary Myelodysplastic Syndrome

Immunoregulatory T and B cell functions in 15 patients with primary myelodysplastic syndrome (MDS) were studied by measuring the proliferative and the stimulatory capacity of T and B cells, respectively, in autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR). T cell proliferation in the auto MLR was 25% of the control (P less than .02), whereas proliferation in the allo MLR was normal. When control T cells were stimulated by MDS B cells, their proliferative response was only 57% of the control (P less than .01). The mechanism responsible for these abnormalities was studied by determining the capacity of MDS and normal T cells to produce interleukin 2 (IL 2) and to generate IL 2 receptors (IL 2R) following stimulation with control and MDS B cells. In the auto MLR of MDS patients, only 3% +/- 2% of T cells developed IL 2R positivity, whereas in control cultures 12% +/- 2% of T cells were positive, as determined by immunofluorescence, using a monoclonal antibody (MoAb) directed against the IL 2R, and FACS analysis. When MDS T cells were stimulated by control B cells, IL 2R generation and the production of IL 2 were within normal limits. In contrast, when control T cells were stimulated by MDS B cells or control B cells, the MDS B cells induced production of only 26% of IL 2 as compared with control B cells. In parallel experiments, IL 2R generation in control T cells stimulated by either MDS or control B cells was similar. We conclude that in the primary MDS, T and B cell interactions are impaired. Although MDS T cells develop normal quantities of IL 2R and produce normal amounts of IL 2 when stimulated by control B cells, they are markedly impaired when stimulated by self B cells. Similarly, MDS B cells can induce IL 2R generation in control T cells but not in MDS T cells. Myelodysplastic B cells are also defective in inducing IL 2 production by normal T cells in an allo MLR. These in vitro abnormalities strongly suggest that generation of lymphocytes with immunoregulatory functions is impaired in patients with MDS.

Lymphocyte interleukin 2 production and responsiveness are altered in patients with primary myelodysplastic syndrome

Immunoregulatory T and B cell functions in 15 patients with primary myelodysplastic syndrome (MDS) were studied by measuring the proliferative and the stimulatory capacity of T and B cells, respectively, in autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR). T cell proliferation in the auto MLR was 25% of the control (P less than .02), whereas proliferation in the allo MLR was normal. When control T cells were stimulated by MDS B cells, their proliferative response was only 57% of the control (P less than .01). The mechanism responsible for these abnormalities was studied by determining the capacity of MDS and normal T cells to produce interleukin 2 (IL 2) and to generate IL 2 receptors (IL 2R) following stimulation with control and MDS B cells. In the auto MLR of MDS patients, only 3% +/- 2% of T cells developed IL 2R positivity, whereas in control cultures 12% +/- 2% of T cells were positive, as determined by immunofluorescence, using a monoclonal antibody (MoAb) directed against the IL 2R, and FACS analysis. When MDS T cells were stimulated by control B cells, IL 2R generation and the production of IL 2 were within normal limits. In contrast, when control T cells were stimulated by MDS B cells or control B cells, the MDS B cells induced production of only 26% of IL 2 as compared with control B cells. In parallel experiments, IL 2R generation in control T cells stimulated by either MDS or control B cells was similar. We conclude that in the primary MDS, T and B cell interactions are impaired. Although MDS T cells develop normal quantities of IL 2R and produce normal amounts of IL 2 when stimulated by control B cells, they are markedly impaired when stimulated by self B cells. Similarly, MDS B cells can induce IL 2R generation in control T cells but not in MDS T cells. Myelodysplastic B cells are also defective in inducing IL 2 production by normal T cells in an allo MLR. These in vitro abnormalities strongly suggest that generation of lymphocytes with immunoregulatory functions is impaired in patients with MDS.

Interleukin 2 induces appearance of LGL/Leu11 + /K562 lytic cells in Leu11 - low density peripheral blood mononuclear cell population

Low density Percoll fraction cells cultured with interleukin 2 (IL-2) showed a higher proportion of large granular lymphocytes (LGL) and higher K562 cytolytic activity, as compared to a culture lacking IL-2. Furthermore, in a negatively selected Leu11-population, derived from low density cells, cultured for 7 days in medium supplemented with lymphocyte (L) or recombinant (R) IL-2, there appeared LGL and Leu11 + cells. Moreover, some level of K562 lytic activity and higher proportion of DR + and Tac + cells was found as compared to lacking IL-2 culture. Cytofluorograph analysis of cells labelled with propidium iodide revealed that a proportion of the low density Leu11 − starting cell population entered the growth cycle while cultured with IL-2. In addition was found that Leu11 + cells evolve during culture with IL-2 into population lacking in part this phenotype marker. The present work shows that precursors of K562 cytolytic cells lacking Leu11 antigen reside in low density cell fraction, and that they may differentiate in LGL/Leu11 + cells.

Suppression of interleukin 2 production in an animal model of thermal injury is related to prostaglandin synthesis.

We performed studies using an animal model of thermal injury to confirm the observed decrease in interleukin 2 (IL-2) production in burned patients and to explore the underlying mechanisms. Ten mice subjected to a 25% scald were compared with ten anesthetized littermates (controls) and six untreated mice (normal mice) 1, 3, 5, 7, 10, 14, and 21 days after burn. Production of IL-2 by splenocytes was stimulated by concanavalin A alone, or in the presence of the cyclooxygenase inhibitor indomethacin or flurbiprofen. The IL-2 content of the resulting supernatant was determined by the response of the IL-2-dependent cell line CTLL-2. The IL-2 production was significantly suppressed in the burned mice at three days (mean +/- SEM, 30.9% +/- 5.2%), five days (19% +/- 5.5%), seven days (41.6% +/- 6.4%), and 21 days (20% +/- 4.5%). Significant enhancement of IL-2 production by indomethacin was seen in the burned group (mean, 95%), but not in controls (mean, 23.8%) or normal mice (mean, 17.2%), and similar effects were seen with flurbiprofen. In separate experiments the effects of exogenous prostaglandin E2 on lymphocyte blastogenesis and IL-2 production were studied, and an increased susceptibility to the inhibitory effects of prostaglandin E2 was observed following thermal injury.

Interleukin-2 inhibition of oligodendrocyte progenitor cell proliferation depends on expression of the TAC receptor.

Interleukin-2 (IL-2) has been shown to inhibit oligodendrocyte progenitor cell proliferation. Within the immune system, IL-2 biological action is dependent strictly on the expression of the IL-2 receptor. The antibody TAC, which specifically binds the lymphocyte IL-2 receptor, has been shown to also bind oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium. The expression of the TAC antigen was found necessary for IL-2 inhibition of oligodendrocyte progenitor cell proliferation. After IL-2 induced down-regulation of the TAC antigen, the progenitor cell was unresponsive to IL-2, even 72 hr after IL-2 withdrawal. During this unresponsive period, the oligodendrocyte progenitor cell was immunocytochemically negative for the TAC antigen. Thus, in contrast to IL-2 receptors on T-cells, IL-2 does not up-regulate its receptor on oligodendrocyte progenitor cells. However, upon interleukin 1 (IL-1) addition both IL-2 responsiveness and TAC immunocytochemical staining reappeared. These data suggest that IL-2 inhibition of progenitor cell proliferation depends on the expression of the TAC antigen, which can be regulated by IL-1.