Cloning of a novel cell type from human fetal liver expressing cytoplasmic CD3 delta and epsilon but not membrane CD3.

Seventeen-week human fetal liver cells cultured with a feeder cell mixture of irradiated PBL, irradiated JY cells (an EBV-transformed B cell line) and PHA contained a subpopulation of CD3- cells in addition to a major population of T cells with the mature phenotype. After 12 days in culture, CD3- CD16- cells were sorted and cloned by limiting dilution. Two representative clones, FL121 and FL125, were expanded and characterized. They shared the phenotype of CD2+CD3-CD4-CD5-CD6+CD16-CD56+. FL121 did not express CD8 whereas FL125 expressed CD8 alpha but not CD8 beta. Both clones were found to express cytoplasmic CD3 delta and CD3 epsilon Ag while CD3- NK clones isolated from PBL were negative for them. These results indicate that FL121 and FL125 were committed to the T-cell lineage. Southern blot analysis showed that the TCR beta genes and the TCR gamma genes of these clones were in the germ-line configuration. The establishment of FL121 and FL125 may provide a novel insight into the earliest stage of T-cell development in man.     

Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto''s disease and subacute thyroiditis.

We examined peripheral lymphocyte subsets in patients with autoimmune thyroid disease, or subacute thyroiditis, in the active stage when possible. During destructive thyrotoxicosis arising from alpha beta T cell receptor (TCR) negative T (WT31-CD3+) cells and CD8 (CD4-CD8+) cells decreased and those of CD4+CD8+ cells increased slightly, resulting in proportional increases in CD4 (CD4+CD8-) cells, non-T, non-B (CD5-CD19-) cells, and the CD4/CD8 cell ratio. Changes were similar in active subacute thyroiditis. During stimulative thyrotoxicosis in active Graves' disease, the numbers of such T lymphocyte subsets were not changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly, resulting in proportional decreases in total T (CD3+) cells, alpha beta+ TCR T (WT31+CD3+) cells, CD8 cells, and non-T, non-B cells. A serial study of some of the patients showed opposite changes in alpha beta TCR- T cells, the CD4/CD8 cell ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's diseases. alpha beta TCR- T cells were mostly gamma delta TCR+ T (IIF2+ CD3+) cells in these patients. These data suggest that alpha beta TCR-T (gamma delta TCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells are important in thyroid stimulation in Graves' disease.     

Proliferative and cytotoxic capabilities of CD16+CD56- and CD16+/-CD56+ natural killer cells

Natural killer (NK) cells can be divided into several subpopulations according to their expression of the surface antigens CD16 and CD56. The modest quantity of NK cells in the blood available for functional analysis has been a limitation in studies of NK cell subpopulations. In the present study, epinephrine infusion was used to induce lymphocytosis before immunomagnetic methods were applied to isolate CD16+/-CD56+ and CD16+CD56- CD3- NK cells. These subpopulations were compared according to their proliferative and cytotoxic capabilities in 10 human immunodeficiency virus (HIV)-infected individuals and 5 healthy controls. The CD16+CD56- NK cell subgroup had a higher proliferative capacity, whereas the CD16+/-CD56+ NK cell subgroup was mainly cytotoxic, and unaffected by HIV serostatus. This study thus suggests that NK cell phenotypes more strongly predict NK cell function than HIV serostatus. This assertion should be considered when studying NK cell function in subjects with a deviating composition of NK cells.     

Importance of CD80/CD86-CD28 interactions in the recognition of target cells by CD8+CD122+ regulatory T cells

CD8+CD122+ regulatory T cells are a newly identified, naturally occurring type of regulatory T cell that produce interleukin-10 (IL-10) and effectively suppress interferon-gamma (IFN-gamma) production from both CD8+ and CD4+ target cells. Molecular mechanisms responsible for the recognition of target cells by CD8+CD122+ regulatory T cells were investigated in this study by using an in vitro culture system that reconstitutes the regulatory action of these cells. CD8+CD122( regulatory T cells did not produce IL-10 and did not suppress the IFN-gamma production of allogeneic target T cells when they were stimulated by immobilized anti-CD3 antibody alone, but they clearly produced IL-10 and suppressed the IFN-gamma production of target cells when stimulated by anti-CD3 plus anti-CD28-coated beads. IFN-gamma production by major histocompatibility complex-class I-deficient T cells was also suppressed by CD8+CD122+ regulatory T cells stimulated with anti-CD3 plus anti-CD28 antibody but was not suppressed by cells stimulated by anti-CD3 alone. Experiments examining the blockade of cell surface molecules expressed on either the regulatory cells or the target cells by adding specific neutralizing antibodies in the culture indicated that CD80, CD86, and CD28 molecules were involved in the regulatory action, but cytotoxic T lymphocyte antigen-4, inducible costimulatory molecule (ICOS) and programmed death-1 (PD-1) molecules were not. Finally, CD8+CD122+ cells isolated from CD28-knockout (CD28-/-) mice showed no regulatory activity. These results indicate that CD8+CD122(+) regulatory T cells recognize target T cells via the interaction of CD80/CD86-CD28 molecules to become active regulatory cells that produce suppressive factors such as IL-10.     

T-Cell Immune Imbalance in Rheumatoid Arthritis Is Associated with Alterations in NK Cells and NK-Like T Cells Expressing CD38

BackgroundCD38+ NK (CD3− CD16+ CD38+ CD56+) cells were increased in rheumatoid arthritis (RA), which suppressed Treg cell differentiation. This study explored how CD38+ NK cells regulated CD4+ T-cell differentiation into Treg cells in RA.MethodsProportions of CD38+ NK cells and their counterpart CD38+ NK-like T (CD3+ CD16+ CD38+ CD56+) cells were measured in RA and rats with collagen-induced arthritis (CIA). CD38+ NK cells and CD38+ NK-like T cells were cocultured with CD4+ T cells, respectively.ResultsA significantly increased proportion of CD38+ NK cells and a decreased proportion of CD38+ NK-like T cells were detected in RA and CIA blood and synovial fluids. When CD4+ T cells were cocultured with CD38+ NK cells, mammalian target of rapamycin (mTOR) signaling was activated, and Th1/Th2 and Th17/Treg ratios were increased. When CD38+ NK cells were pretreated with anti-CD38 antibody, Treg cell proportion was increased, and Th1/Th2 and Th17/Treg ratios were decreased. CD38+ NK-like T cells showed the opposite results. CD38+ NK cells and CD38+ NK-like-T cells activated differential gene expressions and pathways in CD4+ T cells and initiated Th1 and Th2 cell differentiation by differential gene nodes.ConclusionsThis study suggest that the high CD38+ NK cell proportion and low CD38+ NK-like T cell proportion in RA suppress Treg cell differentiation by stimulating mTOR signaling in CD4+ T cells, which consequentially disturbs the immune tolerance.     

Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease.

Intrathyroidal lymphocyte subsets were analysed in 13 euthyroid patients with autoimmune thyroid disease by two-colour flow cytometry and compared with subsets in peripheral blood. In both Graves' and Hashimoto's diseases, proportions of intrathyroidal CD5- B cells were higher than in peripheral blood. The numbers of such cells were correlated with serum levels of anti-thyroid microsomal antibodies. Proportions of T cells bearing alpha beta chains of T cell receptors (TCR alpha beta+ T; T alpha beta) and CD16+CD57+ natural killer (NK) cells were lower in the thyroid, but proportions of CD3hiTCR alpha beta-TCR gamma delta+ (T gamma delta) cells were not different. Proportions of CD4+Leu-8- helper T cells and CD4+CD57+ germinal centre T cells were higher and proportions of CD4+Leu-8+ suppressor-inducer T cells and CD8+CD57+ or CD8+CD11b+ suppressor T cells were lower than in the blood in both diseases. Proportions of CD5+ B cells were high in Graves' disease, and proportions of CD8+CD11b- cytotoxic T cells were high in Hashimoto's disease. Unexpectedly, CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells were present in thyroid tissues of both diseases. These findings suggest that: (i) an imbalance in the numbers of regulatory T cells and of NK cells that had appeared in the thyroid resulted in the proliferation of CD5- B cells, which were related to thyroid autoantibody production; (ii) CD5+ B cells and cytotoxic T cells are important for the different pathological features in Graves' and Hashimoto's diseases, respectively; and (iii) intrathyroidal CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells may be related to the pathogenesis of autoimmune thyroid disease.     

结核性胸液中NK细胞的亚群及表型功能特征分析

目的探讨结核性胸液(PFC)中NK细胞的亚群分布及表型功能特征。方法以正常人外周血单个核细胞(PBMC)作对照,利用多种标记抗体进行表面和细胞内细胞毒效应分子染色,再利用流式细胞仪在单个细胞水平上分析结核性胸水中NK细胞亚群的异质性和生物学特征。结果 NK细胞可以分为CD56+CD16-、CD56+CD16+和CD56-CD16+三个亚群,与PBMC中的NK细胞相比,PFC中CD56+CD16-NK细胞亚群明显增加,而CD56+CD16+NK细胞亚群比例明显下降;结核性胸液中CD56+CD16-及CD56+CD16+NK细胞亚群表达较低水平的颗粒酶B,CD107a/b的比例在结核性胸液中3个NK细胞亚群中均有增加(P<0.05)。结核性胸液中NK细胞表达高水平表面抑制性受体NKG2A及表面活化性受体NKG2D。活化分子CD69及CD25在结核性胸水中NK细胞上的表达均有所增加(P<0.05)。结论结核性胸液中的NK细胞比例与PBMC相比发生变化,结核性胸液中的NK细胞表达低水平杀伤分子颗粒酶B但表达高水平活化分子CD69,提示NK细胞在结核感染中发挥其生物学功能。     

Expression of CD11b (Leu15) antigen on CD3+, CD4+, CD8+, CD16+ peripheral lymphocytes. Estimation of CD3+8+11b+ and CD3+4-8-11b+ T-cell subsets using a single laser flow cytometer.

CD11b (Leu15) epitope is expressed on 20-30% of peripheral blood lymphocytes, including CD16+ large granular lymphocytes and CD8+ cells. This study confirms that 30% of CD8+ lymphocytes and virtually all CD16+ NK cells from healthy subjects express this determinant. In parallel, our data show that various proportions of CD3+4-8-, TCR-delta cytotoxic T lymphocytes and occasionally CD4+ lymphocytes subsets could also express this epitope. The CD8+11b+ phenotype is associated with suppression of T-cell proliferative response and has been extensively used to characterize suppressor T lymphocytes. Since about 25% of CD8 lymphocytes are non-T (CD3-) and express the CD16 NK antigen (CD8+16+3-), the expression of CD11b was also studied on CD8+3+ T-cell and CD8+16+ NK-cell subsets. To this end, we developed three methods using a flow cytometer equipped with a single laser and two fluorescence detectors. Results showed that T CD8+3+11b+ and NK CD8+16+11b+ lymphocytes account for 30% and 70% of CD8+11b+ cells respectively. Consequently, the CD8+3+11b+ phenotype would be more specific for suppressor T lymphocytes than the total CD8+11b+ phenotype which includes high proportions of CD16+ NK cells.     

Accumulation of CD16-CD56+ natural killer cells with high affinity interleukin 2 receptors in human early pregnancy decidua.

Most human peripheral blood natural killer (NK) cells express the phenotype CD16+CD56+. However, a very minor subset of NK cells express CD16-CD56+, and these NK cells bear both interleukin 2 receptor (IL-2R)alpha (p55) and IL-2R beta (p75) (high affinity IL-2 receptors). In this report, we demonstrate that in human early pregnancy decidua--an interface between maternal immunocompetent cells and fetus (placenta)--abundant (approximately 83%) CD16-CD56+ NK cells with high affinity IL-2 receptors were present, and these cells responded to low amounts of IL-2 (4.5 pM). These CD16-CD56+ NK cells significantly expressed an early activation antigen, CD69, in vivo, whereas peripheral CD16-CD56+ NK cells did not express CD69. These findings suggest that CD16-CD56+ NK cells in early pregnancy decidua may be activated in vivo, and may play an important role in immunoregulation during early pregnancy. Also, decidual lymphocytes may be useful materials to study the mechanism of MHC-unrestricted cytotoxicity of this type of NK cells.     

CD28 is not directly involved in the response of human CD3- CD56+ natural killer cells to lipopolysaccharide: a role for T cells

We have previously shown that human CD3- CD56+ and CD3+ CD56+ cells from some individuals mount vigorous proliferative responses to lipopolysaccharide. Such responses have been blocked by the presence of cytotoxic T-lymphocyte antigen-4 immunoglobulin fusion protein in the cultures, implicating a role for B7-mediated costimulation. Here we confirm this inhibition of natural killer (NK) expansion using antibodies against B7-1 and B7-2. We were unable to specifically detect CD28 on the surface of resting or stimulated human peripheral blood NK cells, however, in either lipopolysaccharide-responsive or non-responsive individuals, using a panel of four different anti-CD28 monoclonal antibodies. T-cell depletion from peripheral blood mononuclear cell cultures resulted in a reduction in the induction of CD25 on activated CD3- CD56hi cells and in the expansion and proliferation of CD3- CD56+ NK cells. Furthermore, reconstitution experiments using peripheral blood dendritic cells and purified NK cells demonstrated that NK expansion could only be achieved in the presence of purified T cells.     

外周血CD3~+CD56~+T细胞在恶性肿瘤患者中的表现及临床意义

目的了解 CD3+ CD5 6 + T细胞与 CD3- CD5 6 + 、CD3+ CD5 6 - 的关系及其在参与恶性肿瘤患者抗肿瘤免疫中的作用。方法采用流式细胞术对 10 0例恶性肿瘤患者 (5 5例实体瘤患者和 45例非实体瘤患者 )及 46例健康对照组外周血中的 CD3+ CD5 6 +、CD3- CD5 6 +、CD3+ CD5 6 - 3类淋巴细胞进行标记分析。结果在实体瘤和非实体瘤患者组中 :CD3+ CD5 6 + T细胞均有高表达 ,2组患者与健康对照组比较均有显著性差异 (P<0 .0 1)。 CD3+ CD5 6 - T细胞在实体瘤组的表达都显著低于非实体瘤组和健康对照组 ,2组间比较均有显著性差异 (P<0 .0 0 1) ;而 CD3- CD5 6 + NK细胞在 2患者组中的表达与健康对照组比较均无显著性差异 (P>0 .0 5 )。结论 CD3+ CD5 6 + T细胞在恶性肿瘤患者外周血中的高表达较 CD3- CD5 6 + NK细胞更明显 ,并且不受恶性肿瘤细胞类型的影响 ,提示高表达的 CD3+ CD5 6 + T细胞是参与抗肿瘤免疫的重要表现     

Selective expansion and engraftment of human CD16+ NK cells in NOD/SCID mice

NK cells are large granular lymphocytes that represent a critical component of the innate immunity. Investigations of human NK cell function are largely based on in vitro assays because of the lack of suitable animal models. Here we have established conditions leading to the development of human NK cells in NOD/SCID (severe combined immunodeficiency) mice receiving grafts of cord blood mononuclear cells (CBMC), and GFP-transduced HFWT inducing NK cells (GHINK-1), which have been shown to support the selective expansion of NK cells from human PBMC and CBMC in vitro. Significant numbers of CD56dimCD16+ cytotoxic and CD56-CD16+ immature NK cells appeared in peripheral blood (PB), peritoneal cavity, spleen, bone marrow and liver of the mice. The newly generated NK cells did not express activation markers such as CD25, CD69 and NKp44, the expression of which was augmented by IL-2 in vitro. The NOD/SCID mice engrafted with human NK cells exhibited antitumor activity against K562 erythroleukemia in vitro and in vivo. Thus, we succeeded in developing a CD56dimCD16+ cytotoxic NK cell populations in NOD/SCID mice closely resembling the main NK fraction in human PB and CD56-CD16+ immature NK cells. Our model provides not only information about the development and dynamics of physiological human NK cells but also an important pre-clinical system for immunotherapeutic strategies.     

The co-expression of 2B4 (CD244) and CD160 delineates a subpopulation of human CD8+ T cells with a potent CD160-mediated cytolytic effector function

Within human CD8+ T lymphocytes, the CD27-CD45RAhigh or CD56+ phenotypes contribute to precisely define the cells with CTL effector function. Novel markers were demonstrated to correlate with CTL properties, such as the 2B4 (CD244) receptor, a member of the CD2 subset of the immunoglobulin superfamily or the glycosylphosphatidylinositol-anchored CD160 receptor. We performed a study of these markers to further define the population of effectors with CTL functions. Here we show that cytotoxic subpopulations defined by surface markers CD160, CD56 and CD57 are mostly contained in the 2B4+CD8+ T cell population. Expression of CD160 identifies two populations in the 2B4+ population. The 2B4+CD160+ subset expresses a bona fide CTL phenotype. The co-expression of 2B4 and CD160 defines T cells containing high amounts of perforin and granzyme B. During CTL ontogeny, an up-regulation of 2B4 and CD160 is observed from a naive to a terminally differentiated phenotype. Finally, we demonstrated that CD160 triggering failed to induce cytotoxicity per se, but costimulated CD3-redirected killing. We conclude that the co-expression of 2B4 and CD160 defines a CD8+ T lymphocyte subpopulation with high CTL activity.     

Systematic characterization of human CD8+ T cells with natural killer cell markers in comparison with natural killer cells and normal CD8+ T cells

We investigated the function of CD56+ CD8+ T cells (CD56+ T cells) and CD56- CD57+ CD8+ T cells (CD57+ T cells; natural killer (NK)-type T cells) and compared them with those of normal CD56- CD57- CD8+ T cells (CD8+ T cells) and CD56+ NK cells from healthy volunteers. After the stimulation with immobilized anti-CD3 antibodies, both NK-type T cells produced much larger amounts of interferon-gamma (IFN-gamma) than CD8+ T cells. Both NK-type T cells also acquired a more potent cytotoxicity against NK-sensitive K562 cells than CD8+ T cells while only CD56+ T cells showed a potent cytotoxicity against NK-resistant Raji cells. After the stimulation with a combination of interleukin (IL)-2, IL-12 and IL-15, the IFN-gamma amounts produced were NK cells > or = CD56+ T cells > or = CD57+ T cells > CD8+ T cells. The cytotoxicities against K562 cells were NK cells > CD56+ T cells > or = CD57+ T cells > CD8+ T cells while cytotoxicities against Raji cells were CD56+ T cells > CD57+ T cells > or = CD8+ T cells > or = NK cells. However, the CD3-stimulated proliferation of both NK-type T cells was smaller than that of CD8+ T cells partly because NK-type T cells were susceptible to apoptosis. In addition to NK cells, NK-type T cells but not CD8+ T cells stimulated with cytokines, expressed cytoplasmic perforin and granzyme B. Furthermore, CD3-stimulated IFN-gamma production from peripheral blood mononuclear cells (PBMC) correlated with the proportions of CD57+ T cells in PBMC from donors. Our findings suggest that NK-type T cells play an important role in the T helper 1 responses and the immunological changes associated with ageing.     

A lymphocyte differentiation and activation antigen, CZ-1, that distinguishes between CD8+ and unstimulated CD4+ T lymphocytes.

We report the generation and cellular reactivity of a novel rat IgM monoclonal antibody (mAb), CZ-1, made against mouse natural killer (NK) cells activated in vivo. mAb CZ-1 recognizes a molecule whose properties are consistent with that of a trypsin-sensitive, non-phosphatidyl inositol-linked sialoglycoprotein. The expression of the antigen recognized by mAb CZ-1 is restricted mostly to cells of the lymphoid lineage. The antigen is expressed on 10%-25% of bone marrow cells and 3%-5% of thymocytes. Analysis of thymocyte subpopulations indicates expression of the CZ-1 antigen on 100% of the NK1.1+, 27% of the CD4-CD8-, 1.1% of the CD4+CD8+, 1.1% of the CD4+CD8-, and 33% of the CD4-CD8+ cells. In the spleen, the CZ-1 antigen is expressed on B lymphocytes, NK cells, and virtually all CD8+ T lymphocytes. Most unstimulated CD4+ splenic T lymphocytes, monocytes and polymorphonuclear cells, with the notable exception of basophils, do not react with mAb CZ-1. CD4+ T cells activated in vivo by virus infection or in vitro by anti-CD3 and interleukin-2 express the CZ-1 antigen. These results indicate that mAb CZ-1 identifies a novel inducible lymphocyte activation/differentiation antigen that distinguishes between thymic and unstimulated splenic CD4+ and CD8+ T lymphocytes. This mAb will be a useful tool in the identification of lymphocyte subpopulations and in the study of the ontogeny and activation of these cells.     

Suppressive role of NK cells in pokeweed mitogen-induced immunoglobulin synthesis: effect of depletion/enrichment of Leu 11b+ cells.

Natural killer (NK) cells probably have immunoregulatory effects. However, the evidence to date is mainly based on the suppressive effect of enrichment with relatively impure NK populations (large granular lymphocytes, LGL, Leu 7a+ cells). Here we report on the effect of enrichment and depletion of Leu 7a+ and Leu 11b+ cells (the latter containing virtually all NK activity in freshly prepared lymphocytes) on pokeweed mitogen (PWM)-induced immunoglobulin (Ig) synthesis. Enrichment suppressed Ig synthesis to a degree dependent on the number of cells added, and was not enhanced further by their pretreatment with interferon. Furthermore, depletion of Leu 11b+ cells from peripheral blood lymphocytes (PBL) led to marked enhancement (2-25-fold increase) of Ig synthesis, suggesting these cells may normally exert a suppressive effect. The possible underlying mechanisms were investigated further. Enhanced Ig synthesis by Leu 11b-depleted cultures was associated with an increased number of Ig-secreting cells by plaque assay, but with no change in numbers of CD4+ or CD8+ cells. Treatment of PBL with monoclonal antibodies (anti-Leu 7a/Leu 11b) alone suppressed PWM-induced immunoglobulin synthesis. We conclude that NK cells play a role in the regulation of Ig production, at least in part by an effect on activation/differentiation of B cells, but independent of altered T-cell subpopulations. The effect may be unrelated to their cytotoxic function (being unaffected by interferon, IFN), although the direct effects of anti-Leu 11b and Leu 7a in enhancing the suppressive effect suggest an alternative activation pathway.     

Cytotoxicity of human natural killer (NK) cell subsets for Plasmodium falciparum erythrocytic schizonts: stimulation by cytokines and inhibition by neomycin.

Quantification of human peripheral blood NK subsets has been made in a group of Kenyan adults and children with acute P. falciparum malaria. Results were compared with data obtained from three age- and sex-matched control cohorts: parasitaemic but asymptomatic children; aparasitaemic children and adults; and adult Caucasians with no previous history of malaria. Separated NK subsets were tested in vitro for cytotoxicity to erythrocytic schizonts of P. falciparum in the presence and absence of cytokines. There was a statistically significant quantitative and qualitative depression of the CD3-CD56+ subset in patients with acute malaria and this was accompanied by an expansion of the 'non-functional' CD3-CD57+CD16-CD56- subset. Both CD3-CD16+ and CD3-CD56+ NK cells from all patients and donors lysed schizonts, and this cytotoxicity was enhanced by the addition of recombinant interferon-alpha and/or IL-2, notably with the CD3-CD56+ subset. Interestingly, asymptomatic donors had the highest levels of CD3-CD56+ NK cells, which also demonstrated an enhanced response to cytokine stimulation. Cytotoxicity to schizonts was accompanied by the release of soluble NK cell lytic factors. Neomycin suppressed cytotoxicity in a dose-dependent manner, indicating that the lysis of schizonts by NK cells involves phospholipase C-mediated phosphoinositide metabolism. Our findings define a role for NK cells in immunity to malaria through the lysis of infected erythrocytes as a first-line defence against the parasite.     

The temporal redistribution pattern of NK cells under acute stress based on CD62L adhesion molecule expression

Recent studies demonstrated that an acute psychological stressor elicited transient changes in lymphocyte redistribution. Earlier studies had established that CD3-CD16+CD56+ natural killer cells (NK cells) increased remarkably in peripheral blood circulation and that the amount of lymphocyte redistribution in NK cells was dependent on the CD62L expression density. Specifically, CD62L- cells were mobilized more pronouncedly than were CD62L+ cells. These results led us to hypothesize that such different reactivity causes different temporal characteristics between CD62L+ and CD62L- lymphocyte subsets. The present study was conducted to examine this issue. Ten female participants experienced a 10-minute baseline period and performed a 10-minute mental arithmetic task as an acute psychological stressor. Blood samples for measuring the proportions of CD62L+ or CD62L- NK cells and CD62L+ or CD62L- T cells were obtained immediately after each period and every 2 min during the task. As expected, CD62L+ and CD62L- NK cells showed different reactivity in response to the stressor and showed different temporal characteristics. That is, the elevation of CD62L- NK cells reached a significant level at 1 min after the initiation of the stressor, while CD62L+ NK cells took 8 min to show a tendency of elevation. Although CD3+ T cells showed different reactivity between CD62L cell types, they did not show different temporal characteristics. These findings suggest that the expression of CD62L modulates not only the amount of redistribution but also the temporal characteristics of the redistribution of NK cells.