Cord blood CD4(+)CD25(+) regulatory T cells fail to inhibit cord blood NK cell functions due to insufficient production and expression of TGF-beta1.

Although CD4(+)CD25(+) Treg (Treg) cells are known to modulate NK cell functions, the modulation mechanism of these cells in cord blood has not been fully clarified. The purpose of this study was to clarify the mechanism whereby cord blood Treg cells modulate cord NK cells. By performing various cultures of purified NK cells with or without autologous Treg cells, diminished inhibitory effects of cord Treg cells towards cord NK cell functions, including activation, cytokine production, and cytotoxicity, were observed. We also observed lower secretion of sTGF-beta1 and lower expression of mTGF-beta1 by cord Treg cells than by adult Treg cells. These data revealed the capability of adult Treg cells to suppress rhIL-2-stimulated NK cell function by TGF-beta1, both membrane-bound and soluble types. The reduced inhibitory capabilities of cord Treg cells compared with adult Treg cells is thought to be due to insufficient expression of TGF-beta1.

Blunted heart rate circadian rhythms in small for gestational age infants during the early neonatal period.

Infants born with intrauterine growth restriction are at increased risk for adverse cardiovascular outcomes in neonatal and later life. Although circadian rhythm is a prognostic marker of cardiovascular health, the concern over the circadian rhythm of these infants is rarely observed. To determine the influence of intrauterine growth retardation on the pattern of circadian rhythm, heart rate (HR) circadian rhythmicity was analyzed in 39 small for gestational age (SGA; birth weight and height below <-2.0 standard deviation score [SDS]) and 117 appropriate for gestational age (AGA; >-1.5 to <1.5 SDS) infants within 72 hours of birth using spectral analysis and cosinor analysis. Amplitude, midline estimating statistic of rhythm, and acrophase calculated from circadian rhythm were analyzed with clinical variables. A significant HR circadian rhythm was observed in 23.1% of the SGA and 24.8% of the AGA group without significant differences; however, SGA infants exhibited remarkable smaller amplitudes compared with AGA in all gestational age (GA) groups (p < 0.001). Amplitudes in AGA infants were positively correlated with the GA or body composition relevant variables (p < 0.001, respectively), but not SGA infants. The blunted HR circadian rhythmicity in SGA infants showed in this study might indicate the vulnerability to pathophysiological condition and could potentially refer to cardiovascular disease in later life.

Phosphoinositide 3-kinase induced activation and cytoskeletal translocation of protein kinase CK2 in protease activated receptor 1-stimulated platelets.

CK2 is a highly conserved protein kinase involved in several cellular events. CK2 is expressed in platelets but its role in platelet activation remains poorly understood. In the present study, we tested the hypothesis that CK2 plays a role in platelet activation, particularly in the PAR1-dependent signal transduction pathway. The effect of CK2 and PI 3-kinase inhibitors on aggregation of platelets, activation of GPIIb/IIIa, activation and translocation of CK2 was examined. Platelets were incubated with the cell permeable CK2 inhibitors, DRB, DMAT and TBB and stimulated with the PAR1-AP (SFLLRNP). CK2 inhibitors showed the specific inhibitory pattern of platelet aggregation, characterized by a primary phase of aggregation followed by progressive disaggregation. CK2 inhibitors suppressed the activation of GPIIb/IIIa. PAR1-AP induced two-fold increase in CK2 activity and stimulated the translocation of CK2 from Triton X-100-soluble to -insoluble fraction. Preincubation of platelets with the PI 3-kinase inhibitor, wortmannin or LY294002, impaired PAR1-AP-induced aggregation of platelets. PAR1-AP-induced increase in CK2 activity and translocation of CK2 were inhibited by these treatments. Taken together, the present study demonstrated, for the first time, that PI 3-kinase-CK2 pathway plays an important role in the mechanism of PAR1-dependent platelet aggregation.

Developmental trends in mother-infant interaction from 4-months to 42-months: using an observation technique.

BACKGROUND: It is clear that early social interaction follows from mother-infant interaction after pregnancy. Many researchers have illuminated this interaction in the first years of life. Most common mother-infant interaction is the attachment behavior of an infant. The Japan Children's Study (JCS) development psychology group hypothesis is that the early mother-infant interaction will predict later social behaviors. But the method applied to evaluate this interaction mainly comes from the evaluation of the whole observation situation and is dependent upon the coder. We applied a new observational method that checked the on/off status of behavior and recorded sequentially. METHODS: Using a semi-structured observation setting as our method, we analyzed the developmental change of mother-infant interaction within a toy situation. RESULTS: The result indicated that mother-infant interaction with a toy altered at around 9-months and is salient to the usual developmental change of joint attention. Additionally cluster analysis suggested that the developmental pattern is divided into two clusters. This is the first report on a developmental pattern of joint attention. CONCLUSIONS: These results indicated that the developmental trend of gaze direction and vocalization is one candidate of measure for evaluating the mother infant social interaction from the point of joint attention.

Mission in Sukusuku cohort, Mie: a study focusing on the characteristics of participants and the mental health of the mothers raising children.

BACKGROUND: We carried out Sukusuku cohort, Mie (SCM), a long term cohort study of child development and investigated the feasibility and validity of this study. Then we focused on the characteristics of the enrolled families and verified the representativeness of the participants in SCM. METHODS: The characteristics of 185 families recruited from 3 hospitals were analyzed, and we verified the representativeness of these subjects. We also analyzed the factors that may influence the mental health of the mothers who are raising children. RESULTS: There were no significant differences between the subjects from the 3 hospitals in terms of the age distribution, academic background, occupation, and annual income of the participating families. At 42 months, the average developmental quotients for postural and motor, cognitive and adaptive, and speech and social development in the 140 infants were 98.6, 100.6, and 99.9, respectively. The overall developmental quotient for infants was 100.3 +/- 13.2; this score was within the standard range (55-132). The path-analysis model revealed that family function was an important factor influencing the mental health of mothers. CONCLUSIONS: The participant characteristics were thought to be generally representative, and we showed the validity and representativeness of the participants in this cohort study. The mental health analysis of mothers suggested that relieving mothers from child-rearing stress and maintaining family function were important for the maintenance and improvement of maternal mental health.

Mission in Sukusuku cohort, Mie: focusing on the feasibility and validity of methods for enrolling and retaining participants.

BACKGROUND: We investigated the feasibility and validity of and systematized the methods used to enroll and retain participants requiring long-term interdisciplinary collaborations. We carried out this study in the Sukusuku cohort, Mie (SCM), as one of the regional research site of Japan Children's Study (JCS). METHODS: A total of 467 families who were screened between December 1, 2004 and December 31, 2005, in the Mie-chuo Medical Center and 2 other hospitals; these families were deemed eligible for the study. Of these, a total of 185 families (39.6%) participated in the 4-month observation. Of these families, 5 dropped out at month 9 of the observation; 9, at month 18; 17, at month 30; and 5, at month 42. The retention rates at 9, 18, 30, and 42 months of observation were 97.3%, 92.4%, 83.2%, and 80.5%, respectively. Reinstatement to a previous job was the most common reason for dropouts. RESULTS: We observed that informative consultation notes during observation were beneficial for the retention of participants, and these notes also helped in improving communication between the study subjects and the evaluators during subsequent visits. CONCLUSIONS: In this study, we did not perform the standard checks for child development alone but also investigated the motivating influence of research partnerships with participants. Further, these visits help maintain the motivation levels of the participants and encourage them to contribute for social causes. The results present integration models that can be applied in future relevant longitudinal cohort studies in Japan.

Cerebral oxygenation responses during kangaroo care in low birth weight infants.

BACKGROUND: Kangaroo care (KC) has been widely using to improve the care of low birth weight infants. However, very little is known about cerebral hemodynamics responses in low birth weight infants during KC intervention. The objective of this study was to elucidate the response of cerebral hemodynamics during KC in low birth weight infants. METHODS: Near infrared spectroscopy measured regional cerebral oxygenation (rSO2), heart rate (HR), respiration rate (RR) measured by electrocardiogram, and percentages of oxygen saturation (SpO2) measured by pulse oxymetry was monitored in 16 preterm infants (< 1600 g) in three sessions: before, during, and after KC. Using power spectral analysis, total power (TP), low-frequency (LF, 0.02-0.20 Hz) and high-frequency (HF, 0.20-0.50 Hz) bands, the ratio of LF/HF were calculated and normalized as %LF or %HF = LF or HF/TP x 100 (%). RESULTS: Significant differences were not observed in the mean rSO2, HR, and SpO2 throughout sessions; however, the TP of these parameters was significantly decreased during KC and increased after KC (p < 0.001). The %LF of LrSO2 and RrSO2 was decreased during KC (p < 0.05) with decreased %HF in RrSO2 (p < 0.05). The %LF of HR was significantly increased during KC while %HF was decreased (p < 0.05). Mean and TP of RR was increased during KC (p < 0.01 respectively) with the increase of quiet sleep state (p < 0.05) and decreased after KC (p < 0.01). The %LF of RR was increased after KC (p < 0.05) with decreased %HF (p < 0.05); however, significant changes were not observed during KC. CONCLUSION: KC intervention appears to have influence on cerebral hemodynamics as well as cardiorespiratory parameters. The results of rSO2 and HR might be associated with quiet sleep states. The results of this study may indicate the contribution of KC intervention to the activation of central nervous system and brain function. Further study is needed to determine the underlying physiology responsible for these differences.

Infant responses to maternal still-face at 4 and 9 months.

This study investigated developmental changes in infant responses to maternal still-face (SF) situations. Infants (21 males and 25 females) of Japanese mothers were observed in a face-to-face SF paradigm, comprising four phases (normal/SF/normal/SF), at two infant ages (4 and 9 months). The infants' facial expression, gaze direction, and vocalization were coded in both SF and normal interaction conditions. The results indicated that infants at both ages showed a decrease in displaying positive facial expression and gazing at their mothers during SF conditions. The 4-month-old displayed emotional expression and directed their gaze toward their mothers more frequently than the 9-month-old. However, the 9-month-old vocalized more often in SF situations, attempting to elicit responses from their mothers. The "carry-over" effect was observed only in 9-month-old. The results were discussed in the context of developmental changes in infants' social skills to cope with an emotionally stressful situation.

A nuclear factor-kappaB inhibitor pyrrolidine dithiocarbamate ameliorates pulmonary hypertension in rats.

BACKGROUND: Pulmonary hypertension (PH) is a fatal disorder that is associated with structural changes and inflammatory responses in the pulmonary vasculature. Nuclear factor (NF)-kappaB is a key transcription factor that is involved in the tissue remodeling mediated by inflammatory and fibroproliferative responses. However, the contribution of NF-kappaB-mediated inflammatory pathways to the development of PH is unknown. METHODS: We therefore investigated whether NF-kappaB activation and the expression of a downstream product vascular cell adhesion molecule (VCAM)-1 is associated with pulmonary vascular diseases in rats that have been injected with the toxin monocrotaline (MCT), and whether a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), ameliorates such diseases in rats. RESULTS: VCAM-1 expression and the nuclear localization of the p65 subunit of NF-kappaB, as analyzed immunohistochemically, was significantly up-regulated in the endothelium of diseased vessels on the days 8 to 22 (p < 0.05). Next, 39 rats were divided into three groups (rats injected with MCT and treated with saline solution or PDTC, and controls similarly treated with saline solution). Compared to controls, MCT treatment increased the mean (+/- SE) pulmonary artery pressure (31.2 +/- 1.4 mm Hg [p < 0.05] vs 22.8 +/- 0.9 mm Hg, respectively), which was reduced by PDTC treatment (24.3 +/- 1.2 mm Hg; p < 0.05). Indexes of right ventricular hypertrophy and pulmonary vascular diseases induced by MCT were similarly inhibited (p < 0.05), which was associated with the suppression of VCAM-1 expression and macrophage infiltration. CONCLUSIONS: We concluded that the NF-kappaB nuclear localization and VCAM-1 expression is temporally and spatially associated with the development of MCT-induced PH in rats, which was ameliorated by administering a NF-kappaB inhibitor, PDTC.

Identification of alpha-1L and alpha-1A adrenoceptors in human prostate by tissue segment binding.

PURPOSE: Silodosin (KMD-3213 or [(-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide]) (Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan) is a selective antagonist for alpha-1A and alpha-1L adrenoceptors. Using this tritiated ligand the 2 alpha-1 adrenoceptors were examined in binding studies with intact tissue segments and membrane preparations of human prostate, and compared with functionally identified alpha-1 adrenoceptor. MATERIALS AND METHODS: Binding assays with tissue segments and membrane preparations of human prostate samples were performed using [3H]-silodosin and binding affinities for various drugs were estimated. In functional experiments antagonist affinities were evaluated from the inhibitory potency against the contractile response to noradrenaline. RESULTS: [3H]-silodosin bound to intact segments and membrane preparations of human prostate with subnanomolar affinity. [3H]-silodosin binding sites in intact segments were divided into 2 distinct components with different affinities for prazosin and RS-17053 (N-[2(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl1H-indole-3-ethanamine hydrochloride) (Research Biochemicals International, Natick, Massachusetts), while binding in membrane preparations showed single high affinity for these drugs. [3H]-silodosin binding sites also showed high affinity for silodosin and tamsulosin but low sensitivity to BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione) (Research Biochemicals International) in intact segments and in membrane preparations. In functional experiments silodosin and tamsulosin potently inhibited the contractile response to noradrenaline but prazosin, RS-17053 and BMY 7378 showed low antagonistic affinity. CONCLUSIONS: The current binding studies in human prostate samples clearly show that alpha-1L and alpha-1A adrenoceptors coexist as pharmacologically distinct entities in intact tissues but not in crude membrane preparations. Also, alpha-1 adrenoceptors involved in the contractile response to noradrenaline are the alpha-1L subtype.

Emergence of physiological rhythmicity in term and preterm neonates in a neonatal intensive care unit.

BACKGROUND: Biological rhythmicity, particularly circadian rhythmicity, is considered to be a key mechanism in the maintenance of physiological function. Very little is known, however, about biological rhythmicity pattern in preterm and term neonates in neonatal intensive care units (NICU). In this study, we investigated whether term and preterm neonates admitted to NICU exhibit biological rhythmicity during the neonatal period. METHODS: Twenty-four-hour continuous recording of four physiological variables (heart rate: HR recorded by electrocardiogram; pulse rate: PR recorded by pulse oxymetry; respiratory rate: RR; and oxygen saturation of pulse oxymetry: SpO2) was conducted on 187 neonates in NICU during 0-21 days of postnatal age (PNA). Rhythmicity was analyzed by spectral analysis (SPSS procedure Spectra). The Fisher test was performed to test the statistical significance of the cycles. The cycle with the largest peak of the periodogram intensities was determined as dominant cycle and confirmed by Fourier analysis. The amplitudes and amplitude indexes for each dominant cycle were calculated. RESULTS: Circadian cycles were observed among 23.8% neonates in HR, 20% in PR, 27.8% in RR and 16% in SpO2 in 0-3 days of PNA. Percentages of circadian cycles were the highest (40%) at < 28 wks of gestational age (GA), decreasing with GA, and the lowest (14.3%) at > or = 37 wks GA within 3 days of PNA in PR and were decreased in the later PNA. An increase of the amplitude with GA was observed in PR, and significant group differences were present in all periods. Amplitudes and amplitude indexes were positively correlated with postconceptional age (PCA) in PR (p < 0.001). Among clinical parameters, oxygen administration showed significant association (p < 0.05) with circadian rhythms of PR in the first 3 days of life. CONCLUSION: Whereas circadian rhythmicity in neonates may result from maternal influence, the increase of amplitude indexes in PR with PCA may be related to physiological maturity. Further studies are needed to elucidate the effect of oxygenation on physiological rhythmicity in neonates.

[Alpha1-adrenoceptor subtypes and alpha1-adrenoceptor antagonists].

Alpha(1)-adrenoceptors are widely distributed in the human body and play important physiologic roles. Three alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) have been cloned and show different pharmacologic profiles. In addition, a putative alpha(1)-adrenoceptor (alpha(1L) subtype) has also been proposed. Recently, three drugs (tamsulosin, naftopidil, and silodosin) have been developed in Japan for the treatment of urinary obstruction in patients with benign prostatic hyperplasia. In this review, we describe recent alpha(1)-adrenoceptor subclassifications and the pharmacologic characteristics (subtype selectivity and clinical relevance) of alpha(1)-adrenoceptor antagonists.

Discrimination of acute graft-versus-host disease from infections by enumeration of peripheral blood interferon-gamma spot-forming cells.

Infections may coexist and in certain circumstances aggravate acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. Early detection of aGVHD is often difficult in patients with concurrent infections. Using an enzyme-linked immunospot assay that reflects ongoing immune status in vivo, we enumerated spot-forming cells (SFCs) for interferon (IFN)-gamma, interleukin (IL)-4, and IL-12 in peripheral blood from 56 patients with hematological disorders. Eleven patients had viral, fungal, or bacterial systemic infections during first 10 weeks posttransplant. Of these, six patients with grade 0-I aGVHD showed normal levels of IFN-gamma SFCs. On the other hand, IFN-gamma SFCs were elevated in five patients with grade II-IV aGVHD. These data indicate that increased IFN-gamma SFCs seemed to be correlated with clinically significant aGVHD, but not with infection itself. IL-4 and IL-12 SFCs increased in some patients with infections, irrespective of the presence of aGVHD. Thus, IFN-gamma SFCs may be used to distinguish systemic infections from aGVHD.

Quantifying receptor properties: the tissue segment binding method - a powerful tool for the pharmacome analysis of native receptors.

The radioligand binding assay technique is an extremely powerful tool for studying receptors. It allows an analysis of the interactions of hormones, neurotransmitters, and related drugs with their receptors. Most of the binding assays have widely been applied to crude membrane fractions prepared from many tissues, but in the conventional method, there are some limitations such as a yield loss of receptor-bearing membranes and a change in receptor environment upon homogenization and fractionation. Recently, in order to overcome these problems, a binding assay has been developed using intact tissue segments. This article presents a brief overview of the tissue segment binding assay that has been developed mainly in our department. Practical guidelines for setting up this new assay are presented, including segment preparation, choice of appropriate radioligand, optimizing assay conditions, and appropriate methods for data analysis. The unique advantages and disadvantages of the tissue segment binding method are discussed in comparison with those of conventional membrane binding methods. We suggest that the tissue segment binding method is a powerful tool for detecting the native properties of receptors occurring in tissues and cells without altering their environment.

Prediction of acute graft-versus-host disease and detection of distinct end-organ targets by enumeration of peripheral blood cytokine spot-forming cells.

BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. It was hypothesized that type 1 cytokines promoted aGVHD and type 2 cytokines inhibited it. However, recent publications demonstrated contradictory results in murine models. Type 1/2 paradigm in aGVHD remains to be determined in human. METHODS: Using enzyme-linked immunospot assay that reflects ongoing immune status in vivo, we measured spot-forming cells (SFCs) for interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 in peripheral blood from 56 patients with hematological disorders who underwent allogeneic hematopoietic stem cell transplantation. RESULTS: The numbers of IFN-gamma and IL-4 SFCs in patients with grade II approximately IV aGVHD were significantly higher than those in patients with grade 0 approximately I aGVHD. The enumeration of cytokine SFCs predicted aGVHD approximately 4 days before it became clinically evident, since IFN-gamma SFCs in asymptomatic phase that later progressed into grade II approximately IV aGVHD were elevated in 8 out of 8 evaluable patients. Similarly, IL-4 SFCs were elevated in 6 of 8 patients. In addition, Type 1 cytokine SFCs contributed to the intestinal, but not skin and hepatic aGVHD. CONCLUSIONS: Enzyme-linked immunospot assay is clinically useful for predicting aGVHD and detecting distinct end-organ targets following allogeneic hematopoietic stem cell transplantation.

Identification of alpha-1L adrenoceptor in rabbit ear artery.

The alpha-1L adrenoceptor (AR) was identified in rabbit ear artery by both functional and ligand binding studies. In functional studies using arterial rings, the contractile response to NS-49 [(R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluorometh-anesulfonanilide hydrochloride] (alpha-1A and alpha-1L AR-selective agonist) was competitively antagonized with low affinities by prazosin, RS-17053 [N-[2-(2-cyclopropylmethoxyphenoxy) ethyl]-5-chloro-alpha,alpha-dimethyl-1H-indole-3-ethamine hydrochloride], and 5-methylurapidil but with high affinities by tamsulosin and KMD-3213 [(-)-1-(3-hydroxypropyl)-5-[(2R)-2-([2-[(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide]. In contrast, the response to noradrenaline (nonselective alpha-1 AR agonist) was inhibited noncompetitively by these antagonists (except 5-methylurapidil) with Schild slopes different from unity. These results suggest that the response to NS-49 was mediated predominantly via alpha-1L ARs, whereas the response to noradrenaline was produced through two distinct alpha-1 AR subtypes (presumably alpha-1B and alpha-1L ARs). In binding studies with intact segments of rabbit ear artery, [3H]KMD-3213 bound with high affinity (pKD=9.7) to alpha-1 ARs, which were subdivided by prazosin, RS-17053, and 5-methylurapidil into two subtypes (alpha-1A and alpha-1L ARs). In contrast, [3H]prazosin binding sites in ear artery segments (pKD = 9.8) were identified as alpha-1A and alpha-1B ARs. In conventional binding studies using isolated rabbit ear artery microsomal membranes, [3H]KMD-3213 binding sites were identified as alpha-1A ARs with high affinities for prazosin, RS-17053, and 5-methylurapidil. Our study indicates that an alpha-1L AR having a unique pharmacological profile coexists with alpha-1A and alpha-1B ARs in rabbit ear artery and can be identified either functionally or by binding studies using intact tissues but not microsomal membrane preparations.

Expression of short-form caspase 8 correlates with decreased sensitivity to Fas-mediated apoptosis in neuroblastoma cells.

Disruption of apoptotic death signal transduction pathways may be responsible for tumor formation, progression and resistance to treatment in neuroblastoma. Caspase 8, one of the initiator caspases, plays an important role in the Fas-Fas ligand pathway. This caspase signals through the formation of a death-inducing signaling complex in response to Fas activation by its ligand. In this study, we evaluated the sensitivity of a series of human neuroblastoma cell lines to membrane-bound Fas ligand induced-cell death, as well as the expression of Fas, caspase 3 and caspase 8. Sensitivity to Fas-mediated cell death did not correlate with the expression of Fas in neuroblastoma cells, but was directly associated with the pattern of caspase 8 protein expression. We found that the majority of neuroblastoma cell lines we evaluated lacked caspase 8 expression, and these cell lines were invariably resistant to Fas-mediated cell death. In contrast, cell lines expressing normal caspase 8 protein were quite sensitive to Fas-mediated cell death. More interestingly, a group of cell lines expressing a distinct short form of caspase 8 with splicing out of exon 3 consistently showed moderate sensitivity to Fas-mediated cell death. These results indicate that the profile of caspase 8 expression is an important determinant of the response of neuroblastoma cells to Fas-mediated cell death.

The role of donor age in naive T-cell recovery following allogeneic hematopoietic stem cell transplantation: the younger the better.

The high incidence of opportunistic infections after unrelated bone marrow transplantation has been reported. Delayed lymphocyte recovery may be associated with opportunistic infections. Immune reconstitution is influenced by recipient age and graft-vs-host disease. However, the role of donor age is largely unknown. When the effect of donor age on lymphocyte reconstitution post-transplant was examined in the murine allogeneic hematopoietic stem cell transplantation, the recovery of CD4+ naive T-cells in early post-transplant period was correlated inversely with donor age. Clinically, recipient mice transplanted from younger donors showed significantly higher survival rate and mitogenic responses than adult donors. Since CD4+ naive T-cells are mainly involved in primary immune responses to newly encountered antigens and play an important role in host defense, faster recovery of CD4+ naive T-cells in younger donors may contribute to the reduced mortality in early post-transplant period. Therefore, it is better to choose a younger donor if sufficient cell dose is available. In this review, age-related changes in hematopoiesis and lymphopoiesis as well as thymus-dependent and thymus-independent pathways following allogeneic hematopoietic stem cell transplantation are discussed.