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PubMed2002

Longitudinal follow-up of lymphocyte subsets during the first year of life.

A longitudinal study of lymphocyte subsets during infancy was evaluated by using the flow cytometric immunophenotyping method. Two hundred and thirteen blood samples were obtained from 92 healthy, full-term infants of the following ages: 1-7 days old (n = 43), 3 months old (n = 55), 6 months old (n = 57) and 11 months old (n = 58). The absolute numbers of CD3+ and CD3+/CD4+ T lymphocytes increased from birth to 3 months of age, and remained stable thereafter. The absolute number of CD3+/CD8+ T lymphocytes increased from birth to 11 months of age. The absolute number of CD19+ B lymphocytes and NK cells increased rapidly (3 months) after birth and continued to increase throughout the study period. However, the changes in the relative counts of lymphocyte subsets did not always correspond with the changes in their absolute numbers. These results demonstrate the age-related changes in lymphocyte subpopulations and provide reference ranges for lymphocyte subsets during infancy.

Age Factors↗
PubMed1998

Age-related changes in major lymphocyte subsets in cynomolgus monkeys.

Age-related changes in major lymphocyte subsets were analyzed in 195 cynomolgus monkeys (Macaca fascicularis) aged from one month to 31 years. The percentages of CD20+ B cells in peripheral blood lymphocytes (PBL) decreased with age to five years of age, but after that, no significant change was observed. The percentages of CD16+ NK cells gradually increased during the first five years and reached the peak at from four to ten years of age, whereas the percentages of CD3+ T cells in PBL were relatively constant throughout the life. Among the T cells, the CD4+ CD8- T cells decreased, but CD4- CD8+ T cells increased within the first decade of life. We further analyzed the expressions of CD28 and CD29 molecules on T cells to determine the relation between age-related activation and phenotypic changes. Almost all CD4+ CD8- T cells (> 90%) were CD28+ at all ages analyzed, but a clear age-related decrease in CD28 expression was demonstrated in CD4- CD8+ T cells during the first ten years. In the case of CD29 expression, age-related increases in CD29hi cells were apparent in both CD4+ CD8- and CD4- CD8+ T cells during the first ten years. The percentages of CD29hi cells, however, were higher in CD4- CD8+ T cells than in CD4+ CD8- T cells in all ages analyzed. These results indicated that the age-related changes in percentages of major lymphocyte subsets as well as in phenotypes of T cells might be related to the maturation of the immune system including an increase in memory cells in cynomolgus monkeys.

Aging↗
PubMed2001

Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi.

BACKGROUND: Reference lymphocyte subset values for African children are lacking. This study documents these values as well as their alterations associated with perinatal and postnatal HIV-1 transmission and with protection from HIV-1 infection. METHODS: Lymphocyte subsets were determined for HIV-1-seronegative nonpregnant women and their children (controls) and for uninfected, perinatally infected and postnatally infected children born to HIV-1-seropositive mothers in Nairobi, Kenya. The mean, median and 5th and 95th percentile values for CD4+ and CD8+ lymphocyte counts and percentages were determined and compared at the age ranges birth to 3 months, 4 months to 1 year, yearly from 1 to 5 years and from 6 to 10 years of age. RESULTS: Among control children counts differed from published values of other populations. In all age ranges, whereas the absolute values were significantly higher than adult values, the percentages were significantly lower. Children perinatally infected with HIV-1 had clearly distinguishable differences in lymphocyte subset percentages by 3 months of age, when the median CD4+ percentage was 27.9% (5th to 95th percentile, 25.7 to 30.1%) for infected vs. 35.9% (33.3 to 38.7%) for uninfected and 39.9% (37.8 to 42.2%) for control children, P < 0.001; whereas the median CD8+ percentage was 37.0% (33.1 to 41.0%) for infected vs. 27.5% (24.2 to 30.8%) for uninfected and 27.5% (24.2 to 30.8%) for control children, P = 0.001. Differences between uninfected and control children disappeared after 1 year of age. CONCLUSIONS: Normal lymphocyte subset values among African children differ from those in other populations. Significant differences are detectable by 3 months of age in CD4+ and CD8+ lymphocyte percentages among perinatally infected infants, which may be useful as an adjunct in diagnosis. Transient differences observed among HIV-1-exposed but uninfected infants could reflect a successful immune response to HIV-1 challenge.

CD4 Lymphocyte Count↗
PubMed1998

Lymphocyte subsets and adhesion molecules expression in heatstroke and heat stress.

We examined the specificity of the recently reported alterations in circulating lymphocytes in heatstroke by determining lymphocyte subsets in 14 consecutive heatstroke patients before and after cooling and in 7 heat-stressed controls using single- or two-color immunofluorescence flow cytometry. The relationship with catecholamine levels was also studied. In heatstroke, percentages of T (CD3(+)/CD19(-)), T-helper (CD4(+)/CD8(-)), T-inactive [CD3(+)/human leukocyte antigen-DR-], CD11a+, CD11c+, and CD44(+) lymphocytes were significantly decreased, whereas percentages of T-suppressor-cytotoxic (CD8(+)/CD4(-)), natural killer (NK; CD3(-)/CD16(+) or CD56(+)), CD3(+)/CD16(+) or CD56(+), and CD54(+) lymphocytes were significantly increased, compared with 11 normal controls. The changes in the absolute numbers of lymphocyte subsets were in the same direction and were significant for T-helper, T-suppressor-cytotoxic, NK, CD3(+)/CD16(+) or CD56(+), and CD11c+ lymphocytes. Milder but significant changes in percentages of T-helper, T-suppressor-cytotoxic, CD11c+, and CD44(+) lymphocytes were seen in heat stress. Cooling was associated with partial or complete normalization, further derangement (CD11a+, CD11c+), or overcorrection (NK, T-suppressor-cytotoxic, CD11b+) of abnormal percentages of lymphocyte subsets. Norepinephrine levels were significantly elevated in heatstroke (4.7-fold) and heat stress (3.2-fold), but did not significantly correlate with lymphocyte subsets. We conclude that heatstroke is associated with significant changes in percentages and in absolute numbers of a wide range of circulating lymphocyte subsets that are not related to elevated catecholamine levels or totally normalized by cooling. Similar, albeit milder, changes are seen in heat stress, suggesting that the two syndromes represent a continuum.

Antigens, CD↗
PubMed2001

Cutting edge: differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets.

B-1 lymphocytes represent a distinct B cell subset with unusual mitogenic responses. PMA alone promotes proliferation in B-1 cells, but not in splenic B-2 cells. Although cyclin D2-cyclin-dependent kinase 4 (cdk4) complexes mediate early retinoblastoma gene product (pRb) phosphorylation in B-1 cells, the transient nature of their accumulation cannot account for the continued increase in pRb phosphorylation, which is maximal at 24 h. We show herein that PMA promotes the accumulation of functional cyclin D3-cdk4 complexes in B-1 cells following loss of cyclin D2. PMA also induces accumulation of cyclin D3-cdk4 complexes in B-2 cells; however, these complexes do not phosphorylate pRb. Thus, PMA is sufficient to induce synthesis and assembly of cyclin D3-cdk4 complexes in B-1 and B-2 cells; however, PMA triggers cyclin D3-cdk4 activation only in B-1 cells. These results reveal a novel regulatory step that controls activation of cyclin D3-cdk4 complexes whose function segregates differentially in B cell subsets.

Animals↗
PubMed1992

Circulating lymphocyte subsets in second- and third-trimester fetuses: comparison with newborns and adults.

OBJECTIVES: Our objective was to compare the relative sizes of circulating lymphocyte subsets in fetuses, newborns, and adults. STUDY DESIGN: Two-color flow cytometric analysis of lymphocyte cell surface markers was performed on blood from 64 fetuses, 22 newborns, and 67 normal adults. RESULTS: All three groups had similar percentages of CD3+ total T cells, CD4+ helper T cells, CD8+ cytotoxic/suppressor T cells, and CD20+ B cells. Compared with adults, fetuses and newborns had markedly reduced percentages of CD57+ natural killer T cells and consistently increased percentages of CD5+CD20+ B cells. Most fetal and cord T and B lymphocytes expressed the activation marker CD38. CONCLUSIONS: Similarities and age-dependent differences exist among fetal, newborn, and adult circulating lymphocyte subsets. Lymphocyte marker analysis may prove useful in the detection of fetal infection and other complications of gestation.

Adult↗
PubMed1986

T-lymphocyte subsets in patients with squamous cell carcinoma of the head and neck.

T-lymphocyte subsets in the peripheral blood of patients previously untreated for squamous cell carcinoma of the head and neck were investigated using monoclonal antibodies under flow cytometry before starting treatment. T-lymphocyte subsets in the peripheral blood of patients with squamous cell carcinoma did not significantly differ from those in the peripheral blood of healthy subjects, patients with benign tumors of the head and neck, patients with chronic sinusitis and patients with benign otolaryngological diseases. The necessity to investigate the function of T-lymphocyte subsets was suggested. It was furthermore suggested that T-lymphocyte subsets in cancerous tissues should be investigated.

Adult↗
PubMed1994

Circadian variations and prednisolone-induced alterations of circulating lymphocyte subsets in man.

We determined the circadian variations and prednisolone (PSL)-induced alterations of circulating lymphocyte subsets in 10 healthy adults by two-color flow cytometry using monoclonal antibodies to various lymphocyte subsets in order to collect fundamental data for monitoring of the subsets in clinical practice. This study first examined the changes of CD5+ B cells, gamma delta+ or gamma delta-T cells, activated (HLA-DR+) CD4+ or CD8+ cells, CD11b+ or CD11b-CD8+ cells, and natural killer (NK) cell subsets (CD16+CD57-, CD16+CD57+, CD16-CD57+), in addition to other subsets described before. Compared with the base line values obtained at 9:00 (AM) on day 1, lymphocytes, total B cells, CD5+ B cells, total T cells, gamma delta-T cells, CD4+ cells, activated CD4+ cells, CD45RA-CD4+ cells, and activated CD8+ cells were significantly increased at 20:00 (PM). However, the numbers of CD45RA+CD4+ cells, CD11b+ or CD11b-CD8+ cells and three NK cells subsets did not show significant circadian variations. After oral PSL (30 mg), which was given at 7:00 (AM) on day 2, lymphocytes and almost all lymphocyte subsets, except for CD16+CD57- cells, were significantly decreased; these changes recovered between 13 and 26 hours after PSL administration. The circadian variations and PSL-induced alterations of lymphocyte subsets were relatively comparable, but PSL administration cause a decrease in a wider range of lymphocyte subsets including relatively corticosteroid-resistant subsets such as CD45RA+CD4+ cells, CD8+ cell and NK cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Two-color flow cytometry analysis of lymphocyte subsets in patients with acute myocardial infarction and post-myocardial infarction syndrome].

Serial changes in lymphocyte subsets were analyzed in 37 patients with acute myocardial infarction (AMI), in 2 patients with postmyocardial infarction syndrome (PMIS), and in healthy subjects (control group) using two-color flow cytometry to investigate cellular immunity after AMI and PMIS. Peripheral blood lymphocyte subsets were measured on admission and at weeks 2, 4, 8, and 16 after the onset of AMI. The white blood cell count was significantly higher on admission and at week 2 in the AMI group compared with the control group. The percentage of CD4-positive helper T cells was significantly higher on admission and at weeks 2 and 4 in the AMI group compared with the control group, and the percentage of CD8-positive suppressor T cells was significantly lower in the AMI group at week 2 than in the control group. The ratio of helper-to-suppressor T cells peaked 2 weeks after the AMI and then decreased gradually. There were no significant changes in the CD4/CD8 ratio, the percentage of cytotoxic T cells, or the percentage of inducer T cells, throughout the observation period. There were no significant differences in the percentage of T cells, B cells, CD4-positive T cells, CD8-positive T cells, and natural killer cells between AMI patients and control subjects. The percentage of activated CD4- and CD8-positive cells was higher in the AMI group at weeks 4 and 8 than in the control group. There was no significant correlation between changes in lymphocyte subsets and infarct size. The percentage of activated CD8-positive cells was consistently higher in the PMIS group compared with the control and AMI groups. The percentage of cytotoxic T cells in one of the PMIS patients was significantly higher than in the AMI group. There were no significant differences in the proportions of other subsets between PMIS and AMI patients. The changes in lymphocyte subsets observed in patients with AMI suggested that immunological competence was enhanced in these patients. Abnormalities in humoral immunity, such as the appearance of anticardiac antibody, have been observed in patients with PMIS. Our results suggest that PMIS is also associated with changes in cellular immunity.

Adult↗
PubMed2003

Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study.

BACKGROUND: Peripheral blood lymphocyte subsets need to be determined in a large, urban, minority-predominant cohort of healthy children to serve as suitable control subjects for the interpretation of the appearance of these cells in several disease conditions, notably pediatric HIV-1 infection. OBJECTIVE: We sought to determine the distribution of lymphocyte subsets in healthy urban-dwelling infants, children, and adolescents in the United States. METHODS: Lymphocyte subsets were determined by means of 3-color flow cytometry in a cross-sectional study of 807 HIV-unexposed children from birth through 18 years of age. RESULTS: Cell-surface marker analysis demonstrated that age was an extremely important variable in 24 lymphocyte subset distributions measured as percentages or absolute counts--eg, the CD4 (helper) T cell, CD8 (cytotoxic) T cell, CD19 B cell, CD4CD45RACD62L (naive helper) T cell, CD3CD4CD45RO (memory helper) T cell, CD8HLA-DRCD38 (activated cytotoxic) T cell, and CD8CD28 (activation primed cytotoxic) T cell. The testing laboratory proved to be an important variable, indicating the need for using the same laboratory or group of laboratories to assay an individual's blood over time and to assay control and ill or treated populations. Sex and race-ethnicity were much less important. CONCLUSION: The results of this study provide a control population for assessment of the effects of HIV infection on the normal development and distribution of lymphocyte subsets in children of both sexes, all races, and all ethnic backgrounds from birth through 18 years of age in an urban population. This study's findings will also prove invaluable in interpreting the immune changes in children with many other chronic diseases, such as primary immunodeficiency, malignancy, rheumatoid arthritis, and asthma.

Adolescent↗
PubMed1998

[Pathological changes by the imbalance of host T helper lymphocyte subsets in Mycoplasma pulmonis pneumonia of mice].

To evaluate the contribution of the subsets of T helper lymphocyte (Th) to the development of pulmonary lesion in mycoplasma pneumonia, we compared the pathological findings between Th1 dominant mice (C57BL/6) and Th2 dominant mice (BALB/c) in experimental Mycoplasma pulmonis (M. pulmonis) pneumonia. Mice (ICR, C57BL/6, and BALB/c) were intranasally inoculated with 0.03 ml of a solution containing M. pulmonis (1 x 10(8)) colony forming units per ml. Another M. pulmonis inoculated ICR mice were treated with interleukin-2 (IL2; 4.8 micrograms/day), days 3-9, intracutaneously). All mice were sacrificed at day 14, and the lung specimens were examined. Peribronchial lymphocyte cuffing was more prominent in C57BL/6 mice than that of ICR mice, and intra-alveolar inflammatory-cell infiltration in BALB/c mice was more prominent than in ICR mice. Pathological patterns of the lung in IL-2 treated ICR mice were mimicking those of C57BL/6 mice. These results suggested that pathological patterns of mycoplasma pneumonia in mice might be altered by the imbalance of host T helper lymphocyte subset.

Animals↗
PubMed2000

Lymphoproliferative response and T lymphocyte subsets in a medium-term multi-organ bioassay for carcinogenesis in Wistar rats.

The lymphoproliferative response and T lymphocyte subsets were evaluated at different stages of carcinogenesis in male Wistar rats sequentially initiated with N-diethylnitrosamine (DEN), N-butyl-N-4(hydroxybutyl)nitrosamine (BBN), N-methyl-N-nitrosourea (MNU), dihydroxy-di-N-propylnitrosamine (DHPN) and N, N'-dimethylhydrazine (DMH) (DMBDD initiation). One group was evaluated at the 4th week and other initiated group at the 30th week. Two initiated groups were also exposed through diet to 2-acetylaminofluorene (2-AAF) or phenobarbital (PB), from the 6th until the 30th week. Two groups received only 2-AAF or PB until the 30th week. Five groups were studied to evaluate the effects of each initiator. The lymphoproliferative response was induced in vitro by concanavalin A and the percentage of T lymphocyte subsets was determined by flow cytometry. All groups submitted to initiation only, initiation plus promotion, or promotion only, developed significantly more preneoplastic lesions than the untreated control group. The main target organs for tumor development were the liver, colon, urinary bladder, kidneys and Zymbal glands, mainly in the group treated with DMBDD+2-AAF. There were no alterations of the lymphoproliferative response and of the T lymphocyte subsets percentage in the DMBDD-treated group at the 4th and 30th weeks. At the 30th week, the T lymphocyte subsets percentage was also not affected in the initiated groups after treatments with 2-AAF or PB. The lymphoproliferative response, however, was decreased in the DMBDD+2-AAF group and in the groups treated only with 2-AAF or PB. The present results indicate that the initiating chemicals used in the DMBDD initiation protocol do not exert any influence on the immune system. The alteration of lymphoproliferative response induced at the advanced stage of carcinogenesis without alteration of T lymphocyte subsets may indicate that the influence of 2-AAF and PB on the immune system is functional and not toxic.

1,2-Dimethylhydrazine↗
PubMed1983

Lymphocyte subsets in measles. Depressed helper/inducer subpopulation reversed by in vitro treatment with levamisole and ascorbic acid.

Lymphocyte subsets were assessed in patients with measles using the OKT range of monoclonal antibodies. A significant decrease in cells reacting with the OKT3 and OKT4 monoclonal antibodies was observed. When the tests were repeated 3 wk after the acute infection, significant recovery of these subsets was observed. The abnormality in lymphocyte subsets could be reproduced by treating normal lymphocytes with measles virus in vitro. When lymphocytes from patients with measles or when normal cells infected with measles virus in vitro were treated with either levamisole or L-ascorbic acid for 15 min and then retested with the OKT antisera, restoration of the previously depleted OKT3+ and OKT4+ cell population was observed. Ascorbic-acid treatment also, to a certain extent, reversed the inability of measles mononuclear cells to produce lymphocyte mitogenic factor (helper factor for B cells) after pokeweed mitogen activation. This abnormality, however, could not be reversed by in vitro treatment with levamisole. Measles patients treated with L-ascorbic acid demonstrated no accelerated recovery in either their lymphocyte subset profile or their ability to produce lymphocyte mitogenic factor. Although the cause of the depressed OKT3+ and OKT4+ lymphocyte subpopulations in patients with measles is not clear, the results suggest that the effect is not due to an aberration of protein synthesis, but rather to a blocking or steric change produced by the virus on the cell membrane. It is likely that both ascorbic acid and levamisole have the ability to reverse this effect by virtue of their antioxidant properties.

Acute Disease↗
PubMed1997

IgA rheumatoid factor correlates with changes in B and T lymphocyte subsets and disease manifestations in rheumatoid arthritis.

OBJECTIVE: To analyze the relationship between lymphocyte subsets, different rheumatoid factor (RF) isotypes, and clinical features in patients with rheumatoid arthritis (RA). METHODS: Patients with established RA (n = 95) were examined clinically and blood samples were collected for measurements of RF by ELISA and for analysis of lymphocyte subsets by flow cytometry. RESULTS: IgA RF positive patients had more severe disease and higher prevalence of extraarticular manifestations than the other patients. Patients with elevated IgA RF had a higher percentage of CD5+ B cells and of CD4+CD45RO+ T cells compared to the other patients with RA or controls. High percentage of CD4+CD45RO+ T cells was also significantly associated with extraarticular manifestations. Patients with the sicca syndrome had significantly higher ratio of CD5+ B cells than patients without or with other types of extraarticular manifestations. CONCLUSION: Different disease manifestations in RA may be associated not only with certain RF isotypes and RF isotype combinations but also with changes in lymphocyte subsets in the blood. The relative increase of CD4+CD45RO+ T cells in the blood of IgA RF positive patients with RA might reflect preferential recruitment of CD8+CD45RO+ T cells to inflammatory sites.

Adult↗
PubMed1990

[Intrahepatic distribution of lymphocyte subsets and mast cells in patient's liver with hepatolithiasis].

A study of the amount, distribution and proportion of lymphocyte subsets and mast cells in the patient's liver with hepatolithiasis by immunohistochemical techniques found that: (1) The total amount of lymphocyte subsets and mast cells in hepatolithiasis livers was greatly increased. (2) Both cell-mediated immune and humoral immune responses in hepatolithiasis livers were strengthened significantly. (3) There was a disproportion among lymphocyte subsets and abnormal distribution and aggregation of lymphocyte subsets. These changes were possibly related to liver cells damage and hepatic fibrosis.

Antibodies, Monoclonal↗
PubMed1999

Analysis of the peripheral blood lymphocyte subsets in patients with bladder carcinoma.

OBJECTIVES: To evaluate the immune system of patients with bladder transitional cell carcinoma (TCC) by using peripheral blood lymphocyte subsets and to further compare the relationship between these subsets with respect to tumor stage and grade (superficial versus invasive and low versus high grade). METHODS: Thirty patients with superficial TCC of the bladder, 30 patients with invasive TCC of the bladder, and 30 age- and sex-matched control subjects without any malignancy or immunologic abnormality were included in this study. The peripheral blood lymphocyte subset analysis was performed in all patients before any treatment was performed. RESULTS: All lymphocyte subset values of patients with invasive bladder cancer, except B cell value, were significantly lower (P < 0.01) than the values of the control group. There were no significant differences between the lymphocyte subset values of patients with superficial bladder cancer and those of control subjects. The comparison of the lymphocyte subset values of the patients with superficial versus invasive bladder carcinoma revealed that in patients with invasive bladder carcinoma, the numbers of T and natural killer (NK) cells were significantly lower (P < 0.05) than those of patients with superficial bladder carcinoma. Patients with high-grade tumors had significantly fewer (P < 0.05) T and NK cells than patients with low-grade tumors. CONCLUSIONS: Our results indicate that analysis of mean NK and T cell values and the mean ratio of CD4+/CD8+ cells in peripheral blood might be a useful adjunct for the clinical evaluation of patients with bladder cancer.

Adult↗
PubMed1998

Coronary artery disease: changes of blood lymphocyte subsets induced by physical exercise.

To examine the changes in the absolute numbers of blood lymphocyte subsets in patients with coronary artery disease, we studied 26 patients with documented coronary artery disease (group I) and 15 other subjects (group II) with atypical complaints and negative exercise test who served as controls. Blood lymphocyte subsets were determined at rest, immediately and 24 h after a bicycle exercise test. In both groups the absolute number of leukocytes/mm3 and lymphocytes/mm3 was significantly greater immediately after exercise than at rest and returned to baseline values by 24 h post-exercise. The absolute number of B-lymphocytes and CD8+ T-lymphocytes did not change significantly in both groups, while CD3+ and CD4+ T-lymphocytes as well as CD25+ activated T-lymphocytes declined insignificantly immediately after exercise but increased significantly 24 h after exercise in both groups, with a higher increase (P<0.01) in all three variables under study (CD3+, CD4+ and CD25+ T-lymphocytes) in group I in comparison to group II (P<0.05). Our findings showed that changes in lymphocyte subsets induced by physical exercise differ between patients with and without documented coronary artery disease, suggesting that an alteration in immune function may account for these differences.

Aged↗
PubMed1988

Development of lymphocyte subsets in pigtailed macaques.

The early development of eight lymphocyte subsets was determined for pigtailed macaque infants from 0 to 800 days of age using two-color flow cytometry and fluorescein- and R-phycoerythrin-conjugated monoclonal antibodies specific for human leukocyte antigens. Four major lymphocyte subsets in monkeys (B, CD4+ T, CD8+ T, and NK cells) could be further divided using two-color analysis. In neonates, the frequency of lymphocyte subpopulations having surface phenotypes found principally on dense, resting cells (IgD+ B cells, Lp220+ CD4+ T cells, and CD18dull CD8+ T cells) was much higher than subpopulations having phenotypes present principally on buoyant, activated cells (IgD- B cells, Lp220- CD4+ T cells, CD18bri CD8+ T cells). There was a complete absence of two CD18bri CD8+ subsets (CD8dull and CD8bri) during the first 300 days of life. The relative proportion of lymphocyte subsets with resting phenotype decreased with increasing age, while the subpopulations associated with activation gradually increased with age. These findings suggest that during early development immunocompetent cells gradually differentiate into activated lymphocytes.

Age Factors↗