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Immunosuppression after cholecystectomy.

The effect on immune functions of cholecystectomy under combined anaesthesia was studied in nine patients. The parameters examined were the leucocyte and differential count, the T-and B-lymphocyte count, and the lymphocyte transformation induced by phytohaemagglutinin, concanavalin A, pokeweed mitogen and purified protein derivative of tuberculoprotein. The anaesthesia and operation decreased the total lymphocyte count in the peripheral blood. No significant change occurred in the proportion or absolute number of E-binding (T) lymphocytes. The proportion of EAC-binding (B) lymphocytes increased, although no change was observed in the lymphocytes with surface immunoglobulin representing another B-cell marker. A statistically significant decrease was found in the lymphocyte response to all the mitogens used both in cultures with isolated lymphocytes and in whole blood. The changes returned to the pre-induction level on the third postoperative day. These finding suggest a transitory decrease of cell-mediated immunity after cholecystectomy.

Adult↗

Different kinetics of immunologic recovery using nelfinavir or lopinavir/ritonavir-based regimens in children with perinatal HIV-1 infection.

The choice to include the optimal protease inhibitor (PI) in highly active antiretroviral therapy (HAART) regimens in children with perinatal HIV-1 infection is still under debate. Virologic and immunologic outcomes of three different regimens in an observational paediatric cohort were compared. Data from 12 saquinavir-, 18 nelfinavir-, and 10 lopinavir/ritonavir-treated children were analyzed after 4 and 24 weeks of therapy. Immunologic and virologic outcomes were compared using multivariate analysis adjusting the results for age, baseline CD4+ T-lymphocyte count and baseline viral load. Saquinavir-treated children displayed significant reduction in viral load at week 24 (but not at week 4) and no increase in CD4+ T-lymphocyte count, indicating a poor advantage in using this drug. Lopinavir/ritonavir-treated children presented lower viral loads than nelfinavir-treated children at week 4 (P=0.020) and week 24 (P<0.0001). Virologic failure occurred in 6/18 (33.3%) nelfinavir-treated children but in no child receiving lopinavir/ritonavir (P=0.013). An undetectable viral load was achieved in 9/10 (90.0%) lopinavir/ritonavir- vs. 3/18 (16.6%) nelfinavir-treated children (P<0.0001). No significant difference in CD4+ T-lymphocyte count was observed between lopinavir/ritonavir- and nelfinavir-treated children at weeks 4 and 24. However, a different kinetic of the immunologic recovery was observed. Lopinavir/ritonavir-treated children displayed higher CD4+ T-lymphocyte counts than saquinavir-treated children since the first month of therapy (week 4: P=0.042; week 24: P= 0.029) while nelfinavir-treated children took 24 weeks to reach such an outcome (P=0.034). Since lopinavir/ritonavir-based regimen controls viral replication more efficiently and restores CD4+ T-lymphocyte count more quickly than saquinavir- or nelfinavir-based HAART, it may be considered when a salvage therapy or a rapid increase in CD4+ T-lymphocytes is necessary.

Anti-HIV Agents↗

Which one is a risk factor for chemotherapy-induced febrile neutropenia in childhood solid tumors: early lymphopenia or monocytopenia?

Neutropenia is one of the undesirable effects of cancer chemotherapy, sometimes causing life-threatening events. The present study was conducted to identify the risk factors of neutropenia caused by chemotherapy. Between January 2001 and March 2004, a total of 77 children with 165 neutropenic attacks were enrolled in this study. Complete blood count was performed before chemotherapy and on days 1, 3, 5, 7, and 9 consecutively. The complete blood count results of the febrile neutropenia (FN) group were compared to those of the non-FN group. The incidence of FN was significantly higher in patients with ANC counts < or =0.5 x 10(9)/L on days 3, 5, and 7, lymphocyte counts < or =0.5 x 10(9)/L on days 7 and 9, < or =0.7 x 10(9)/L on days 5, 7, and 9, and with monocyte counts < or =0.15 x 10(9)/L on days 7 and 9, respectively. Further statistical analysis showed that lymphocyte count < or =0.7 x 10(9)/L on day 5, and monocyte count < or =0.15 x 10(9)/L on day 7 were independent risk factors for FN. The authors conclude that lymphocyte counts on the 5th day can be more a predictive factor than monocyte count.

Adolescent↗

Cellular immunodeficiency in Paget's disease of bone: changes induced by treatment with elcatonin.

We have found a cellular immune defect (low CD4 T lymphocyte count, high CD8 T lymphocyte count and a low CD4/CD8 ratio) in 39 PDB patients. This finding is not correlated with the bone metabolic activity of the disease. There was an improvement in the cellular immune defect in fifteen patients after treatment with elcatonin. These changes could be related to the improvement in the metabolic derangement or else could be the consequence of an effect on altered immunity.

Aged↗

A controlled trial of bestatin in hydatidiform mole.

A prospective randomized controlled trial was conducted to study whether Bestatin, an immunomodifier, can reduce the incidence of persistent gestational trophoblastic disease in patients with hydatidiform mole. A group of 21 patients (Bestatin group) received 30 mg Bestatin daily after evacuation of the hydatidiform mole. A second group of 23 patients (control group) did not receive any drug. Blood was taken for white cell counts, differential counts, lymphocyte subset counts (CD2+, CD4+, CD8+ and B cells) and natural killer cell activity before evacuation of the hydatidiform moles. The tests were repeated every 4 weeks after evacuation until the serum beta subunit of human chorionic gonadotropin (beta hCG) had returned to normal or until the patient had to receive chemotherapy because of persistent gestational trophoblastic disease. There was no significant difference in the age of the patients, the pre-evacuation serum beta hCG, or the gestational age between the two groups. Chemotherapy was needed by 6 patients in the Bestatin group (28.6%) and 3 patients in the control group (13%) because of persistent gestational trophoblastic disease. There was no significant difference in any of the immunological parameters between the two groups before or after evacuation. We conclude that Bestatin at this dosage does not improve the immunological functions or clinical outcome in patients with hydatidiform mole.

Adjuvants, Immunologic↗

Lymphocyte changes in secondary dengue fever: use of the Technicon H*1 to monitor progress of infection.

Secondary dengue fever as dengue hemorrhagic fever or dengue shock syndrome is a potentially fatal complication of an infection that presents with few clinical signs that help in the diagnosis. Previous workers have reported the value of buffy coat determinations of atypical lymphocytes as an aid to the diagnosis. We report here the use of an automated white blood cell differential counter, the Technicon H*1 in the monitoring of the atypical lymphocyte count as a measure of the progress of the infection in a retrospective study of serial full blood counts in 45 serologically confirmed patients. Technicon H*1 'basophil' and large unstained cell counts and manual atypical lymphocyte counts rose in tandem with the drop in platelets and decreased when the platelets recovered. In a sub-study, the atypical lymphocytes were immunophenotyped and found to be predominantly derived from T lymphocytes. We conclude that the Technicon H*1 is a useful monitor of the activity of the infection in dengue hemorrhagic fever.

Basophils↗

Differentiation and activation antigens on blood mononuclear cells in lymphocytic leukemia before and during IFN-alpha 2B therapy.

Expression of differentiation and activation antigens on peripheral blood mononuclear cells of four chronic lymphocytic leukaemia (CLL) patients was studied before and during interferon-alpha 2b therapy. Patients had clinical stage B(II) disease, a lymphocyte count of over 60 G/l and a lymphocyte doubling time shorter than 12 months. One of the patients unresponsive to previous chemotherapy experienced a substantial decrease of the lymphocyte count during interferon-alpha 2b (IFN-alpha 2b) therapy, with a nadir at one fifth of the initial value while on this therapy. The lymphocyte count decreased slightly in a further patient, while it increased in two patients. Treatment with IFN-alpha 2b left the phenotype of CLL lymphocytes essentially unchanged. The elevated serum beta-2 microglobulin values increased further during treatment with the exception of the CLL patient responsive to IFN-alpha 2b therapy. The clinical stage of the disease did not change in any of the patients when evaluated according to the criteria of the International Workshop on CLL. Further studies are necessary to determine which of the CLL patients benefit from therapy with interferon-alpha 2b.

Adult↗

Circulating anti-tumor and autoantibodies in breast carcinoma: relationship to stage and prognosis.

Serum antibodies to breast tumor antigen(s) and circulating autoantibodies were tested in 175 patients with various stages of carcinoma of the breast, followed for a mean period of 51 months. Antibodies to surface membrane and to cytoplasmic antigens of autologous and allogeneic tumor cells were measured. Peripheral lymphocyte count and skin reaction to six recall antigens were also tested. Patients with metastatic disease had significantly lower prevalence of antibodies to autologous tumor cells and lower total lymphocyte count than patients with early breast cancer. Patients with locally advanced disease (greater than or equal to 4 positive axillary nodes) had the highest frequency of anti-tumor antibodies, the second highest lymphocyte count, but with the lowest prevalance of autoantibodies. Presence or absence of anti-tumor or autoantibody did not correlate with results of skin tests or other standard blood tests. Among patients with locally advanced or metastatic breast cancer, those who had a positive skin test or whose lymphocyte count was 1500 to 2500 per cu mm had significantly better 5-year absolute survival rates (p = 0.04, p = 0.002, respectively). This study suggests that in patients with locally advanced or metastatic breast cancers, skin test reactivity and optimal peripheral lymphocyte count may be useful prognostic indicators. In contrast, neither the presence of anti-tumor antibodies to membrane or cytoplasmic antigens, nor the presence of autoantibodies, correlates with prognosis in patients with early or late breast cancers.

Antigens, Neoplasm↗

Highly active antiretroviral therapy-associated regression of cytomegalovirus retinitis: long-Term results in a small case series.

PURPOSE: To report the stability of acquired immunodeficiency syndrome (AIDS)-associated cytomegalovirus (CMV) retinitis lesions that have undergone regression in the absence of specific anti-CMV medications owing to highly active antiretroviral therapy (HAART)-generated immune recovery. METHODS: The initial examination revealed HAART-associated regression of CMV retinitis lesions in eight subjects at two institutions. Patients were monitored for recurrences of CMV activity. CD4+ T-lymphocyte counts and human immunodeficiency virus (HIV) loads were measured. RESULTS: All patients had positive initial responses to HAART with an average HIV load decrease of 2.26 log units (range 0.3-5.57). Mean CD4+ T-lymphocyte count at baseline was 45.6 (range 4-107) and increased by an average of 132.5 (range 7-266) within the first 2 to 4 months of HAART. Patients were observed for an average of 15.5 months (range 11-20 months). Six subjects had a vigorous and sustained response to therapy, achieving an average HIV load of 9,400 copies/mL (3.32 log10 decrease) and CD4+ T-lymphocyte count of 158.2 cells/microL. These patients had no CMV retinitis progression. By contrast, two others who attained an average log10 decrease of only 0.48 had modest and short-lived increases in the CD4+ T-lymphocyte count. These patients experienced reactivation of CMV retinitis after 5 and 7 months, respectively. CONCLUSIONS: Regressed CMV retinitis may remain healed for long periods. However, failure of HAART to induce substantial decreases in HIV load may predict poor or unsustainable rises in the CD4+ T-lymphocyte count and presage recurrence of CMV retinitis. Vigilance in ophthalmic examinations is especially mandatory in these subjects.

AIDS-Related Opportunistic Infections↗

Pharmacodynamics of FTY720, the first member of a new class of immune-modulating therapeutics in transplantation medicine.

FTY is a novel immunomodulator currently undergoing clinical investigation and has the potential of improving immunosuppressive therapy after organ transplantation. Previous experimental studies in animals have shown that FTY has a unique mechanism of action. We have studied the pharmacodynamic effects of FTY in stable renal allograft recipients taking part in a phase I clinical trial. As in various animal models including non-human primates, a single oral dose of FTY (0.25 - 3.5 mg) significantly reduced peripheral lymphocyte count by 30 - 70%. The peripheral lymphocyte count returned to baseline within 24 hours. Only in those patients treated with the highest dose of FTY (3.5 mg), did peripheral lymphopenia persist for more than 96 hours. FTY reduced all lymphocyte subsets, T cells more than B cells and CD4+ cells more than CD8+ cells. The reduction in CD3+CD62L+ cell counts was more pronounced, whereas CD3+CCR5+ cell counts were less affected in comparison to the total number of CD3+ lymphocytes. We found only slightly increased apoptosis rates (< 5%) in peripheral lymphocytes, and this change does not explain the marked reduction in lymphocyte count. In cultured human lymphocytes only suprapharmacological doses of 10 microM FTY induced apoptosis (20.6 +/- 2.8%) after a 4-h incubation. More important, clinically relevant doses of 0.1 microM FTY increased lymphocyte mobility 2-fold. No effect of FTY on anti-CD3mAb-stimulated lymphocyte proliferation was detected and there was no change in phagocytosis rates in whole-blood cultures incubated with FTY. Further studies are necessary to investigate the mechanism of action of FTY in detail.

Apoptosis↗

Estimation of the temporal probability of human immunodeficiency virus (HIV) dementia after risk stratification for HIV-infected persons.

We developed a scheme using routinely available data to estimate the risk of human immunodeficiency virus (HIV) dementia in HIV-infected persons over time. We performed a longitudinal review of medical records from more than 100 medical facilities in 11 U.S. cities. A total of 19,462 HIV-infected persons without history of dementia enrolled in a multi-institution survey. The main outcome measure was the development of HIV dementia (1987 case definition) during the median follow-up period of 17 months (range, 1 to 72 months). Of 19,462 HIV-infected persons, HIV dementia developed in 880 persons (4.5%; 2.6% per person-year). The strongest predictors of HIV dementia were CD4+ T-lymphocyte count, anemia, and AIDS-defining infections or cancer. The 2-year probability of HIV dementia was highest for persons who had a CD4+ T-lymphocyte count of fewer than 100 cells/microL and an AIDS-defining illness or anemia or both (18.6 to 24.9%). Intermediate risk was observed in persons with CD4+ T-lymphocyte count of 100 to 199 cells/microL and an AIDS-defining illness or anemia or both or in persons with a CD4+ T-lymphocyte count of fewer than 100 cells/microL but without another risk factor (2-year probability, 10.4 to 15.2%). The 2-year probability that HIV dementia would develop was lowest (1.0%) for persons with CD4+ T-lymphocyte count of more than 200 cells/microL and no other risk factors. Risk stratification using routine clinical information provides information that may prove useful in patient care decisions.

AIDS Dementia Complex↗

The walk-in anergic patient. How best to assess the risk of sepsis following elective surgery.

This prospective study evaluated host resistance in a surgical population who walked into the hospital for elective surgery. Patients were stratified into Hospital Reactive (HR, n = 19) if they reacted to two or more of five recall skin test antigens and Walk-in Anergic (WA, n = 26) if they did not react to the antigens. The WA patients were slightly older (74.4 +/- 1.8 years, +/- SEM versus 66.7 +/- 2.7 p less than 0.05). Diagnosis in the HR and WA group were: tumors 13/19 versus 21/26, diverticulitis 3/19 versus 0/19, and miscellaneous 3/19 versus 5/26. Twenty-five laboratory normal controls (LN) were also studied. There were no significant differences in the following parameters between the HR and WA groups: stage of disease; hemoglobin; circulating leukocyte count; polymorphonuclear cell counts; total lymphocyte counts (both groups lower than LN, p less than 0.05), monocyte counts (both higher than LN, p less than 0.05); per cent E-rosettes and lymphocyte blastogenesis to mitogens (phytohemagglutinin, concanavalin-A) and antigens (purified protein derivative and tetanus); phagocytosis of preopsonised Staphylococcus aureus 502A, at 5, 10, and 20 minutes; alpha, beta, and gamma globulins; C3, and total hemolytic complement (CH50) levels; C-reactive protein; and ANA and DNA levels. The HR group demonstrated an increase in the rate of killing of Staphylococcus 502A at 10, 20, 40, and 80 minutes compared to the LN group but the WA group did not show this augmentation (p less than 0.001). The serum albumins were: LN = 4.46, HR = 3.98, WA = 3.43 g/dl (p less than 0.05). Degree and duration of surgery was the same in the HR and WA groups. There were no major sepsis episodes (bacteremia or proven intracavitary abscess) in the HR patients versus 25% in the WA patients (p less than 0.05). There was one death (6%, pulmonary embolus) in the HR group and 8 (40%) in the WA group (p less than 0.05). Antibiotic prophylaxis was equal but the WA patients received therapeutic antibiotics more frequently (65% versus 11% p less than 0.05). Of all the host immunocompetence tests measured in this study, the delayed type hypersensitivity skin test response and the serum albumin were variables abnormal between the survivors and those who died.

Adult↗

Effects of age at seroconversion and baseline HIV RNA level on the loss of CD4+ cells among persons with hemophilia. Multicenter Hemophilia Cohort Study.

OBJECTIVE: To assess the impact of age at seroconversion and HIV RNA level in serum during early chronic infection on the initial values and subsequent trends (slopes) of CD4+ lymphocyte counts. DESIGN AND METHODS: In a cohort of 137 HIV-1-positive hemophiliacs with well-estimated dates of seroconversion, baseline HIV RNA level was measured by reverse transcription PCR in serum specimens collected 12-36 months after the estimated date of seroconversion. Baseline values, 24 months after seroconversion, and slopes of CD4+ lymphocyte counts by age and HIV RNA quartile were examined by fitting random effects models that allowed for intrasubject variability. RESULTS: Both age at seroconversion and HIV RNA level were associated with the CD4+ lymphocyte count at baseline and its subsequent slope. The baseline median CD4+ lymphocyte count was 620 x 10(6)/l. Within each HIV RNA quartile, the median CD4+ cell count of the oldest subjects (age 30-58 years) was about 200 x 10(6)/l lower and at least 350 x 10(6)/l lower than the median counts of the younger (age 11-29 years) and youngest (age 2-10 years) subjects, respectively. Within each age-group, the median CD4+ cell count differed by about 200 x 10(6)/l between subjects in the lowest compared with the highest HIV RNA quartiles. The mean slope of the CD4+ lymphocyte count after month 24 was linear on the square-root scale, steeper in children, and did not vary significantly by baseline HIV RNA quartile. There was large variation between subjects that was unexplained by differences in age and HIV RNA level. CONCLUSIONS: By 24 months after HIV seroconversion, the oldest subjects and those with the highest HIV RNA levels during early chronic infection had experienced the most severe depletion of CD4+ cells. Subsequent declines in CD4+ cells varied little by early chronic HIV RNA level or age.

Adolescent↗

Enhancement of the efficacy of chemotherapy with oxaliplatin plus 5-fluorouracil by pretreatment with IL-2 subcutaneous immunotherapy in metastatic colorectal cancer patients with lymphocytopenia prior to therapy.

The present study was carried out to evaluate the influence of a short-period IL-2 administration on the efficacy of chemotherapy in metastatic colorectal cancer patients with pretreatment lymphocytopenia, which was defined as a lymphocyte count of less than 1500/mm3. The study included 144 consecutive metastatic colorectal cancer patients, who underwent chemotherapy with oxaliplatin plus 5-fluorouracil. Lymphocytopenia was seen in 41/144 (28%) patients, who were randomized to receive chemotherapy alone or chemotherapy after a prechemoimmunotherapy with IL-2 (3 MIU twice/day for 3 consecutive days), whereas patients with a normal pretreatment lymphocyte count received only chemotherapy. A normalization of the lymphocyte number was achieved in 12/19 lymphocytopenic patients pretreated with IL-2. The objective tumor regression rate achieved in patients with a normal lymphocyte count prior to chemotherapy was significantly higher compared to that obtained in lmphocytopenic patients treated with chemotherapy alone (54/103 vs. 3/22, p < 0.01), whereas no significant difference occurred between patients with normal lymphocyte count and lymphocytopenic patients pretreated with IL-2 (54/103 vs. 8/19). This study confirms that pretreatment lymphocytopenia is associated with reduced efficacy of chemotherapy in metastatic colorectal cancer patients. Moreover, it suggests that pretreatment with IL-2 before the onset of chemotherapy may enhance the efficacy of chemotherapy in lymphocytopenic patients. Therefore, the administration of IL-2 before the onset of chemotherapy to improve the immune status of cancer patients may be considered as a new chemoimmunotherapeutic combination, which may be recommended in the treatment of advanced cancer patients, particularly in those with cancer-related immune alterations.

Adult↗

Biomonitoring of genotoxic exposure among stainless steel welders.

A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environmental monitoring of welding fumes and selected metal oxides, biomonitoring of chromium and nickel in serum and urine and mutagenic activity in urine, and evaluation of semen quality were also done. Manual metal arc (MMA) welding and tungsten inert gas (TIG) welding were the dominant welding processes. A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA-AAF)-induced UDS was lower in 23 never-smoking welders than in 19 unexposed never-smokers. Smoking was a confounding factor resulting in significantly higher CA, SCE, NA-AAF binding to DNA and mutagenic activity in urine. Age was also a confounder: CA, SCE, NA-AAF binding to DNA and UDS increased significantly with age. No significant correlation between SCE and CA or between CA and UDS was found. UDS decreased significantly with increasing lymphocyte count and a higher lymphocyte count was seen in MMA welders than in reference persons and in smokers than in non-smokers. Differences in the composition among lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding with MMA is recommended.

Acetoxyacetylaminofluorene↗

The influence of sequential chemotherapy and radiotherapy on mitogen-induced lymphocyte transformation in patients with acute lymphoblastic leukemia.

Although these studies do not allow a definitive differentiation between the relative influence of chemotherapy and radiotherapy on mitogen-induced lymphocyte transformation, the data suggested both radiotherapy and chemotherapy can cause depression; however, radiotherapy may have a more pronounced effect. The relationship between the absolute peripheral blood lymphocyte count and phytohemagglutin and pokeweed mitogen-induced lymphocyte transformation was also analyzed. These data revealed that patients who are receiving or who have received intensive therapy may have normal peripheral absolute lymphocyte counts with impaired lymphocyte transformation. Serial studies of lymphocyte transformation were evaluated in 10 children with acute lymphoblastic leukemia who received both chemotherapy and radiotherapy.

Child↗

Small intestinal intraepithelial lymphocyte levels in cow's milk protein intolerance.

The mean small intestinal intraepithelial lymphocyte count in seven children with untreated cow's milk protein intolerance (CMPI) on a milk-containing diet was significantly higher than 22 control children also having a milk-containing diet. Ten milk-intolerant children on a milk-free diet had a mean intraepithelial lymphocyte count which was significantly lower than the level in the 22 control children on a milk-containing diet. When these 10 children were challenged with cow's milk they relapsed clinically, and in every case the intraepithelial lymphocyte count rose, although it remained within normal limits. Nineteen children on milk-free diets who had recovered from CMPI had a mean lymphocyte count which was also significantly lower than controls on normal diets, suggesting that when milk is remo-ed from the diet the lymphocyte count is low regardless of whether the child is milk sensitive or not. The reaction of intraepithelial lymphocytes to milk in CMPI is markedly different from their response to gluten in coeliac disease.

Animals↗

Effects on immunity of multiple leukapheresis using a rapidly excreted analog of hydroxyethyl starch.

Immunologic studies were performed immediately before and after leukapheresis in five subjects undergoing four granulocyte donations (separated by 3- to 4-week intervals) using continuous-flow centrifugation leukapheresis with a rapidly excreted investigational analog of hydroxyethyl starch. Postleukapheresis donor blood lymphocyte counts and serum immunoglobulin levels decreased transiently, but significantly, during each procedure when compared with preleukapheresis values due simply to plasma volume expansion (acute effects of dilution). Possible long-term effects of repeated procedures were investigated by comparing preleukapheresis values before the first and fourth procedures. Total lymphocyte, total T-lymphocyte, and T4-lymphocyte counts, as well as serum immunoglobulin values and anti-A and B titers measured before the fourth procedure remained unchanged when compared with values obtained before beginning the series of procedures. In contrast, the B-lymphocyte count was decreased, the T8-lymphocyte count was increased, and the T4:T8 ratio was decreased due to the increase in the T8-lymphocyte count. Although statistically significant (p less than 0.05), all changes were slight, and clinically significant effects on donor humoral immunity could not be detected. The mechanisms involved, however, may be of biologic and therapeutic interest.

Antigens, Differentiation, T-Lymphocyte↗