Type I interferon receptors and interferon-τ-stimulated genes in peripheral blood mononuclear cells and polymorphonuclear leucocytes during early pregnancy in beef heifers.

This study characterised the expression of interferon (IFN)-τ-stimulated genes (ISGs) and Type I IFN receptors in circulating polymorphonuclear cells (PMNs) of beef heifers and compared it with expression in peripheral blood mononuclear cells (PBMCs) up to Day 20 of gestation. Nelore heifers (n=26) were subjected to fixed-time AI (FTAI) on Day 0. PMNs and PBMCs were isolated on Days 0, 10, 14, 16, 18 and 20 after FTAI. The abundance of target transcripts (ubiquitin-like protein (ISG15), 2'-5'-oligoadenylate synthetase 1 (OAS1), myxovirus resistance 1 (MX1), myxovirus resistance 2 (MX2), IFN receptor I (IFNAR1) and IFN receptor 2 (IFNAR2)) was determined using real-time quantitative polymerase chain reaction and compared between pregnant (n=8) and non-pregnant (n=9) females. In both PBMCs and PMNs, ISG15 and OAS1 expression was greater in pregnant than non-pregnant heifers on Days 18 and 20. There were no significant differences in the expression of ISGs between PBMCs and PMNs. A time effect on expression was found for IFNAR1 in PBMCs and IFNAR2 in PMNs, with decreased expression of both genes on Days 18 and 20. When the expression of these genes was compared between cell types only in pregnant heifers, IFNAR2 expression in PMNs had an earlier decrease when compared to its expression in PBMCs, starting from Day 18. In conclusion, PMNs do not respond earlier to the conceptus stimulus, and ISG15 and OAS1 expression in both PMNs and PBMCs can be used as a suitable marker for pregnancy diagnosis on Days 18 and 20. In addition, gestational status did not affect IFNAR1 and IFNAR2 expression, but IFNAR2 showed a distinct response between PMNs and PBMCs of pregnant heifers.

Evaluation of positive and false-positive results in syphilis screening of blood donors in Rio de Janeiro, Brazil.

OBJECTIVES: We propose to analyse the positive and false-positive results of treponemal and nontreponemal tests in blood donors from Brazil and to evaluate possible factors associated with the results of treponemal tests. BACKGROUND: Treponemal tests have been used widely for syphilis screening in blood banks. The introduction of these tests in donor screening has caused an impact and a loss of donors who need to be assessed. METHODS: This was a retrospective cross-sectional study of syphilis screening and confirmatory test results of blood donors that were obtained before and after adopting a chemiluminescent immunoassay (CLIA). A comparative analysis was performed using a second sample drawn from positive donors. The possible factors associated with CLIA-positive or CLIA-false-positive results were investigated in a subgroup. Statistical tests were used to compare the proportions and adjusted estimates of association. RESULTS: The reactivity rate increased from 1·01% (N = 28 158) to 2·66% (N = 25 577) after introducing the new test. Among Venereal Disease Research Laboratory (VDRL)- and CLIA-confirmed results, the false-positive rates were 40·5% (N = 180) and 37·4% (N = 359), respectively (P = 0·5266). Older donors (OR = 1·04; P = 0·0010) and donors with lower education levels (OR = 6·59; P = 0·0029) were associated with a higher risk of positivity for syphilis. CONCLUSIONS: CLIA represents an improvement in blood bank serological screening. However, its use in a healthy population appears to result in high rates of false positives. Identifying which characteristics can predict false positives, however, remains a challenge.

Tenofovir plasma concentrations according to companion drugs: a cross-sectional study of HIV-positive patients with normal renal function.

As the risk of tenofovir-associated renal toxicity has been found to be proportional to the drug plasma concentration, our aim was to measure the determinants of tenofovir plasma exposure in HIV-positive patients with normal renal function. A cross-sectional analysis was conducted in HIV-positive patients chronically receiving tenofovir-containing highly active antiretroviral therapies (HAARTs). Patients on tenofovir-containing antiretroviral regimens, presenting 22 to 26 h after drug intake, having estimated glomerular filtration rates above 60 ml/min, reporting high adherence to antiretroviral medications (above 95% of the doses), and signing a written informed consent were included. Plasma tenofovir concentrations were measured through a validated high-performance liquid chromatography-mass spectrometry (HPLC/LC-MS) method. The tenofovir trough concentrations in 195 patients (median, 50 ng/ml, and interquartile range, 35 to 77 ng/ml) were significantly associated with the estimated glomerular filtration rate, body mass index, and third-drug class (protease-containing versus protease-sparing regimens) (with the highest exposure in unboosted-atazanavir recipients). The results of multivariate analysis showed that the third-drug class and the weight/creatinine ratio were independent predictors of tenofovir trough concentrations. This cross-sectional study shows that tenofovir trough concentrations are predicted by the weight/creatinine ratio and by the coadministered antiretrovirals, with protease inhibitors (whether boosted or unboosted) being associated with the highest plasma exposure. These data, previously available in healthy subjects or for some drugs only, could be useful for designing strategies to manage tenofovir-associated toxicity, since this toxicity has been reported to be dose dependent.

Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Effects of estradiol treatments on PGF2α release in beef heifers submitted to estrous resynchronization 14 days after timed-AI.

The effects of 17ß-estradiol (E2) or estradiol benzoate (EB) on PGF2α release were studied in bred-non-pregnant and pregnant Nelore beef heifers. The day of timed artificial insemination (TAI) was designated day 0 (D0), and a single treatment was given on D14. All heifers also received an intravaginal P4 device on D14, and were randomly assigned to three groups: Control (C, P4 device only, n = 12); E2 (1 mg E2 + 9 mg P4, n = 10); or EB (1 mg, n = 10). Blood samples were collected hourly for 8 hours after treatment (Hours 0-8) to measure plasma concentrations (pg/mL) of a PGF2α metabolite (PGFM). The P4 device was removed on D22 and pregnancy was diagnosed on D28. Pregnancy rate was not different among groups (C, n = 7/12; E2, n = 5/10; EB, n = 5/10). More (P < 0.05) heifers had a CV-identified prominent PGFM pulse (peak of > 100 pg/mL) in E2 group (6/10) than in EB (1/10) and C (0/12) groups. Hourly concentration of PGFM for Hours 0 to 8 showed significant effects of group and hour and an interaction of group by hour but did not show an interaction of group or hour with pregnancy status. In preliminary post-hoc analyses, PGFM concentrations during Hours 0 to 8 and pulse characteristics were analyzed within each pregnancy status. For the non-pregnant heifers, a group-by-hour interaction was detected tentatively indicating an increase (P < 0.005) in PGFM concentrations in E2 group from Hours 4 to 6 and in EB group at Hours 5 and 6. Maximum PGFM concentration during Hours 0 to 8 did not differ (P > 0.1) between E2 (124 ± 23) and EB (110 ± 30) groups, but was greater (P < 0.05) in each group than in C (32 ± 3). Furthermore, PGFM concentrations of pulses at the peak, amplitude, and area under pulse curve (pg/mL/h) were greater (P < 0.05) in E2 group than in C group whereas the EB group did not differ (P > 0.1) from the other groups. For pregnant heifers, no effects of group, hour, or their interaction were detected in PGFM concentrations during the hourly sessions, except that maximum PGFM concentration was greater (P < 0.05) in E2 than in EB and C groups. In addition, the number of prominent pulses was greater in E2 group than in Control or EB groups. In conclusion, PGFM increased earlier and in greater concentration combined for bred-non-pregnant and pregnant heifers treated 14 days after TAI with 1 mg E2 plus 9 mg P4 than with 1 mg EB. Tentatively, a positive effect for each of E2 and EB on PGFM concentrations was attenuated in pregnant heifers.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Increased pregnancy rate in beef heifers resynchronized with estradiol at 14 days after TAI.

We aimed to evaluate the treatment with estradiol benzoate (EB) or 17ß-estradiol (E2) associated with progesterone (P4) for resynchronization of ovulation 14 days after timed artificial insemination (TAI). In Experiment 1 (Exp. 1), Nelore heifers were submitted to TAI (D0). On D14, the animals received an intravaginal P4 device and were randomly assigned to one of three groups: control (no treatment; n = 17); EB (1  mg EB; n = 17); and E2+P4 (1 mg E2 + 9 mg P4; n = 18). Ultrasonography evaluations were performed daily from D14 to D22 to map follicular and luteal dynamics. On D22, the P4 devices were removed and non-pregnant (NP) animals were determined using corpus luteum blood flow Doppler ultrasonography. In Exp. 2, 1295 beef heifers were resynchronized and randomly allocated to the same experimental groups as described in Exp. 1. On D22, the largest follicle (LF) was measured in NP and a second TAI was performed on D24. In a subset of heifers (n = 337), an estrus detection patch was used between D22 and D24 to monitor estrus expression and the LF was measured at D24. Confirmatory diagnosis of pregnancy was performed between D37-67 and D43-67 after first and second TAI, respectively. In Exp 1, the proportion of heifers with a synchronized follicular wave emergence (from 3 to 5 days after treatment) was greater (P < 0.05) in the EB group (93.8%) than in the control (62.5%) and E2+P4 (64.7%) groups. Structural luteolysis occurred earlier (P < 0.05) in the EB and E2+P4 groups than in the controls. The pregnancy rate after first TAI did not differ (P > 0.1) among the groups at D22 and at confirmatory diagnosis in both experiments. In Exp 2, the potential pregnancy loss between D22 and D37-67 was similar (P > 0.1) in the control (19% [36/185]), EB (15% [28/182]) and E2+P4 (15% [28/184]) groups. The LF diameter (mm) on D22 was greater (P < 0.05) in the control group (11.9 ± 0.1) than in EB (11.3 ± 0.1) and E2+P4 (11.5 ± 0.1). No difference (P > 0.1) was observed in the proportion of heifers detected in estrus, but LF growth rate (mm/day) between D22 and D24 was greater (P < 0.05) in EB group (0.9 ± 0.08) than in control (0.6 ± 0.07) and E2+P4 (0.7 ± 0.09) groups. The pregnancy rate for the second TAI was greater (P < 0.05) in the EB group (47% [94/200]) than in the control (37% [76/203]), but did not differ (P > 0.1) from the E2+P4 group (43% [93/214]). In conclusion, the treatment with 1 mg EB or 1 mg E2 + 9 mg P4 at 14 days post-TAI anticipates luteolysis in NP heifers but does not compromise pregnancy. The EB treatment induces a new synchronized follicle wave emergence and increases the pregnancy rate of resynchronized NP heifers.

Tuberculosis, COVID-19 and migrants: Preliminary analysis of deaths occurring in 69 patients from two cohorts.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

Laboratory diagnosis of thalassemia.

The thalassemias can be defined as α- or ß-thalassemias depending on the defective globin chain and on the underlying molecular defects. The recognition of carriers is possible by hematological tests. Both α- and ß-thalassemia carriers (heterozygotes) present with microcytic hypochromic parameters with or without mild anemia. Red cell indices and morphology followed by separation and measurement of Hb fractions are the basis for identification of carriers. In addition, iron status should be ascertained by ferritin or zinc protoporphyrin measurements and the iron/total iron-binding capacity/saturation index. Mean corpuscular volume and mean corpuscular hemoglobin are markedly reduced (mean corpuscular volume: 60-70 fl; MCH: 19-23 pg) in ß-thalassemia carriers, whereas a slight to relevant reduction is usually observed in α-carriers. HbA2 determination is the most decisive test for ß-carrier detection although it can be disturbed by the presence of δ-thalassemia defects. In α-thalassemia, HbA2 can be lower than normal and it assumes significant value when iron deficiency is excluded. Several algorithms have been introduced to discriminate from thalassemia carriers and subjects with iron-deficient anemia; because the only discriminating parameter is the red cell counts, these formulas must be used consciously. Molecular analysis is not required to confirm the diagnosis of ß-carrier, but it is necessary to confirm the α-thalassemia carrier status. The molecular diagnosis is essential to predict severe transfusion-dependent and intermediate-to-mild non-transfusion-dependent cases. DNA analysis on chorionic villi is the approach for prenatal diagnosis and the methods are the same used for mutations detection, according to the laboratory facilities and expertise.

The immune response of CBA mice to OSRA, a peripheral protein from the sheep erythrocyte membrane.

The capacity of a membrane protein from sheep erythrocytes (osmotic shock released antigen: OSRA) to elicit an immune response in CBA mice was investigated. While all OSRA preparations tested are antigenically identical en indistinguishable with respect to physicochemical characteristics, they are not equally efficient in stimulating immunocompetent lymphocytes for antibody production upon a primary immunization (immunogenic versus antigenic OSRA). Both antibody-forming and (T and B) memory cells are generated in mice primed with immunogenic OSRA. Evidence is presented that the failure of antigenic OSRA to induce a primary response to SRBC determinants is related to its inability to stimulate unprimed T-cells. OSRA appears to be a major antigenic determinant of the sheep erythrocyte membrane since it specifically inhibits up to 60% of an anti-SRBC response.

Ring 2 chromosome: ten-year follow-up report.

Côté et al. [1981: Ann Genet 24:231-235] suggested that ring chromosomes without a preceding deletion share a common pattern of phenotypic anomalies, independent of what chromosome is involved. The phenotype of such a "general ring syndrome" consists of growth failure without malformations, few or no minor anomalies, and mild-to-moderate mental retardation. We report on a patient with a ring 2 chromosome with features suggestive of Silver-Russell syndrome at birth and striking postnatal growth retardation with minor intellectual involvement supporting Côté's suggestion. This would be the ninth case of ring 2 chromosome published; the patient is the longest reported survivor, with a 10-year follow-up.

Relações interpessoais e sentimentos de acadêmicos emenfermagem na primeira prática hospitalar / Undergraduate nursing students’ interpersonal relationships and feelings in first hospital practice

Objetivo: identificar as relações interpessoais e descrever os sentimentos relatados em fórum dediscussão online por estudantes de Enfermagem durante a primeira prática curricular hospitalar.Método: estudo documental retrospectivo com abordagem qualitativa. Fonte de dados constituídapor 256 registros postados no fórum online, produzidos por 79 estudantes durante o ano de 2013 e oprimeiro semestre de 2014. Dados coletados por download e analisados pelo processo de análise deconteúdo temática. Estudo aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal doRio Grande do Sul. Resultados: categorias: adaptação à rotina e ao ambiente hospitalar, relação como paciente, relação com a equipe, relação com colegas e relação com o professor. Consideraçõesfinais: a presença do professor, o companheirismo entre os colegas, a disponibilidade da equipe ereconhecimento do paciente foram considerados fatores importantes para o estudante. O fórumonline foi o recurso para socialização das vivências.

Objective: identify the interpersonal relationships and describe the feelings reported in onlinediscussion forum by undergraduate nursing students during the first curriculum hospital practice.Methods: it is a retrospective documentary study with qualitative approach. The data sourceconsisted of 256 posting in online forum, produced by 79 students during 2013 and 2014 first half.The data were collected by download and analyzed with thematic content technique. The study wasapproved by Ethics Committee of the Federal University of Rio Grande do Sul. Results: fivecategories were identified: adaptation to the routine and the hospital environmental, therelationship with the patient, the relationship with the staff, the relationship with classmates andthe relationship with the teacher. Final considerations: the teacher’s presence, peercompanionship, team availability, and patient recognition were considered important factors for thestudent. The online forum was identified as resource that facilitated social experiences.

Anamnestic response to a thymus-independent antigen, TNP-LPS in C57BL/6 and DBA/2 mice: dominance of the IgG secondary response of the C57BL/6 mice in the F1 hybrids.

The primary and secondary immune responses to a thymus-independent antigen, TNP-LPS, were investigated in C57BL/6, DBA/2 and (C57BL/6 x DBA/2)F1 mice. While there is no evidence that TNP-LPS induces immunological memory in DBA/2 mice, a definite priming effect has been observed in C57BL/6 mice. Memory is revealed by the appearrance of antibody-forming cells of the IgG isotype. The differentiation of B micron precursors into B gamma memory cells is a dominant phenotype, since it is also found in the F1 C57BL/6 x DBA/2 hybrids.

Cyclosporin A does not affect the in vitro induction of antigen-specific delayed-type hypersensitivity-mediating T cells.

The effect of cyclosporin A (CsA) on the in vitro induction of sheep red blood cell (SRBC)-specific T cells mediating the delayed-type hypersensitivity (DTH) reaction was studied. CsA (1 microgram/ml) addition to the culture medium totally inhibits the in vitro anti-SRBC humoral response but does not interfere with the generation of anti-SRBC DTH-mediating T (TDTH) cells. The induction of TDTH requires the presence of antigen and their expression is mediated selectively by the antigen used in the culture. The TDTH cells generated are Lyt-1+,2- and their induction occurs with a similar efficiency in CsA-treated and untreated cultures: the frequency of the TDTH cells increases by a factor of 10 to 20 during the 6-day incubation period. Lyt-2+ suppressor cells are also generated in CsA-treated or untreated cultures. Our results suggest that a small fraction of T cells can be driven into the proliferative pathway by antigen even in presence of CsA.

Improvement of an ELISA bioassay for the routine titration of murine interferon-gamma.

We improved an ELISA bioassay for murine IFN-gamma (MuIFN-gamma) based on measurement of Ia antigen on P388D1, a mouse macrophagic tumour line. Cells were cultured in microtitre plates in medium containing dilutions of IFN-gamma source. They were then washed and stained with a rat anti-mouse I amAb followed by mouse anti-rat peroxidase-labelled antibody. After incubation with substrate, the OD was read directly from microtitre plates. Standard curves obtained with reference NIH MuIFN-gamma showed that this assay allowed for the definition of unit values (giving 50% of the maximal effect) comparable to NIH international units (IU). It detected as low as 0.2 IU/ml of MuIFN-gamma and, in contrast to antiviral assays, was insensitive to IFN-alpha/beta. We used a concanavalin A-conditioned supernatant, which is a mixed source of lymphokines, to assess the specificity of our assay. Indeed, Ia expression induced by ConA-conditioned supernatant was fully inhibited by preincubation with anti-MuIFN-gamma antibodies. Using a stable indicator cell line, the present cell surface assay is easier to perform than other ELISA using bone-marrow-derived macrophages, and does not require cell fixation; its high sensitivity and specificity are comparable to that of immunoradiometric assays. It is thus valuable for routine MuIFN-gamma quantitations in culture supernatant and biological fluids.

Effect(s) of lipopolysaccharide on lectin-induced T-cell activation.

The present study focuses on the effect of lipopolysaccharide (LPS) on the cellular events leading to T-cell activation by concanavalin A (Con A). Interleukin 2 (Il-2) production is much reduced in Con A-stimulated cultures of spleen cells derived from LPS-treated mice. This depressed Il-2 synthesis is not related to the eventual activity of LPS-activated suppressive B cells. Rather, it reflects an ineffective collaboration between adherent cells and T lymphocytes. The low level of Il-2 produced by LPS-sensitized spleen cells is sufficient for lectin-induced T-cell proliferation. Moreover, acquisition of responsiveness to Il-2 is unaltered by LPS. No strict correlation was found between the deficiency in Il-2 production and the inability of LPS-sensitized spleen cells to generate a thymus-dependent response. Less time (5 hr) is needed for LPS to exert its inhibitory effect on an anti-sheep red blood cell response than on Il-2 synthesis (at least 24 hr). Results are discussed in terms of cellular interactions implicated in a polyclonal T-cell response and with regard to the contribution of Il-2 to the LPS-induced immune unresponsiveness.

Interleukin-2 down-modulates memory T helper lymphocyte development during antigenic stimulation in vitro.

Using an in vitro antigenic stimulation model of murine spleen cells in the presence of the immunosuppressor cyclosporin A (CSA) we have previously reported that not only does this drug not interfere with the differentiation of T lymphocytes into memory cells it appears to favor this differentiation (Motta, I. et al., Eur. J. Immunol. 1991. 21:551). Because CSA blocks interleukin-2 (IL-2) gene expression, we have analyzed the effect of this cytokine on memory T helper cell development. Murine splenic cells were primed for 6 days with sheep red blood cells (SRBC) in protocols in which either IL-2 was not produced or its biological activity was neutralized by anti-IL-2 receptor (R) antibodies. The helper function of the recovered T cells was revealed by their capacity to help virgin B splenocytes produce anti-SRBC antibodies upon challenge in vitro. We found that CD4+ cells primed in the absence of IL-2, provoked either by IL-2 gene transcription blockade by CSA or by treatment with anti-IL-2R antibodies, afford the best helper functions. These cells exhibit a memory-type phenotype characterized by the low expression of the MEL-14 marker and the high expression of the CD44 marker. Evidence is also presented that memory T helper cells originate in part from naive subset displaying the MEL-14hi phenotype. The pattern of expression of the genes encoding different cytokines (IL-2, IL-4, IL-5 and interferon-gamma) following a secondary antigenic stimulation shows that the helper function of the cells primed in the absence of IL-2 correlates with the up-regulation of the IL-2 and the IL-5 genes. From these data, we conclude that IL-2 plays a major role in the control of memory T helper cell induction.