Lymphocyte Subset Populations Research Articles

Treatment of severe atopic dermatitis by topical immune modulation using dinitrochlorobenzene

We present the results of a small uncontrolled pilot trial which suggest that contact sensitization to dinitrochlorobenzene and repeated weekly applications significantly improve the clinical status of severe atopic dermatitis in adults. Although no changes were noted in circulating levels of either lymphocyte subset populations or the serum cytokines assayed in this trial, our observations may be due to topical immune modulation by dinitrochlorobenzene. Larger controlled studies of dinitrochlorobenzene treatment in atopic dermatitis are warranted. (J Am Acad Dermatol 2000;42:687-9.)

Time-Dependent Effect of Cyclosporine on Mitogenic Responses and Lymphocyte Subset Populations in Rat Spleen and Submaxillary Lymph Nodes

Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation and T lymphocyte subsets were measured in spleen and submaxillary lymph nodes of male rats injected with cyclosporine (5 mg/kg s.c. for 5 days, at 12.00 or 24.00 h; animals kept under light from 08.00 to 20.00 h daily). One hour before the third injection, Freund’s complete adjuvant or its vehicle was administered. A suppressive effect of cyclosporine on the mitogenic action of LPS was seen in the spleen of rats injected with cyclosporine at noon whereas the effect of ConA remained unaffected. CD4+, CD8+ and CD4+-CD8+ cells decreased in spleen and lymph nodes of Freund’s adjuvant-injected rats only with cyclosporine given at noon. The results further support occurrence of time-of-day-dependent effects of cyclosporine on lymphocyte subsets and proliferation.

Prospective study of circulating T-lymphocyte subpopulations and disease progression in colorectal cancer.

It has recently been reported that CD4+ T-lymphocytes are reduced in advanced colorectal cancer patients. However, it is not clear whether such changes in T-lymphocyte subsets are an early or late event in such patients. The aim of this study was to examine the relationship between these subsets and disease progression in colorectal cancer. Flow cytometric analysis of T-lymphocyte subsets was performed in 39 patients who, approximately 12 months previously, had undergone surgery for colorectal cancer. These patients were grouped according to whether they developed a recurrence in the following two years. A group of healthy subjects was studied as controls. There was a significant increase in the median neutrophil count (4.3 vs. 3.7 10(6)/ml) and the median numbers of platelets (282 vs. 216 10(6)/ml) of the recurrence group compared with the control group, respectively (P < 0.05). The median numbers (0.28 vs. 0.73 10(6)/ml) and percentage (29 vs. 38 percent) of CD4+ T-lymphocytes of the recurrence group were significantly reduced compared with that of the control group (P < 0.05). There were also reductions in the median percentage of CD3+ cells (67 vs. 74 percent) and the median numbers of CD4+ T-lymphocytes (0.28 vs. 0.46 10(6)/ml) of the recurrence group compared with the no recurrence group (P < 0.05). Reduction of CD4+ T-lymphocytes occurs before detectable recurrence of colorectal cancer. Results of the present study are consistent with impaired immunity, as measured by such lymphocyte subset populations, being important in tumor recurrence in colorectal cancer.

Lymphocyte subsets in relapsing-remitting Multiple Sclerosis: A longitudinal study of B lymphocytes and T lymphocytes

Changes in lymphocyte subset populations may provide clues to the dysimmune mechanisms involved in relapsing remitting multiple sclerosis (RRMS). The lymphocyte subgroup CD4+ CD45RA+, thought to be responsible for the induction of suppression is decreased in some patients with MS compared to controls. A possible role for another lymphocyte subset, CD19+CD5+ lymphocytes, has been proposed in autoimmune diseases and multiple sclerosis (MS). To expand this we studied CD4+CD45RA+ (T) lymphocytes and CD19+CD5+ (B) lymphocytes in nine patients with relapsing-remitting MS (RRMS) and nine controls. The patients were examined monthly for an average of ten months and nine relapses were observed in seven patients. One patient underwent monthly gadolinium enhanced magnetic resonance imaging (MRI). Normal percentages CD4+CD45RA+ lymphocytes were found in patients with RRMS. No significant abnormalities in the CD19+CD5+ lymphocyte subpopulation were noted, although a tendency for higher percentages of this subset (approaching statistical significance, P = 0.056) was detected.

Role of Carotenoids in the Immune Response

The well-established provitamin A activities of certain carotenoids have hampered past research into their possible specific functions. More recently, research interests on carotenoids have been revived, largely because of their anticancer activities. β-Carotene and other carotenoids have been reported to possess immunomodulatory activities in humans and animals. These carotenoids enhance lymphocyte blastogenesis, increase the population of specific lymphocyte subsets, increase lymphocyte cytotoxic activity, and stimulate the production of various cytokines. In addition, carotenoids also stimulate the phagocytic and bacteria-killing ability of blood neutrophils and peritoneal macrophages. The action of these carotenoids is widely accepted to be independent of their provitamin A activity. The immunostimulatory action of carotenoids may be translated into improved health, including mammary and reproductive health in dairy cattle. More studies are needed to establish fully the beneficial effects of supplementation of different carotenoids on the health of dairy cattle. Furthermore, studies on carotenoids other than β-carotene are needed.

Immunohistochemical characterization of the lymphocyte and the immunoglobulin-containing cell in the epithelium and the lamina propria of normal human intestines.

In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig)-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum) of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu2a), helper/inducer T (Leu3a), suppressor T (Leu15) and natural killer/K (Leu7) cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs) were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.

A multicellular tumor spheroid model of cellular immunity against head and neck cancer.

A multicellular tumor spheroid (MTS) model for head and neck cancers has been used to examine the immune function of fresh and 6-day interleukin-2(IL-2)-activated peripheral blood lymphocytes (PBL). MTS are individually cultured in the presence of effector cells, and the spheroids' growth is monitored by sizing them under an inverted microscope. Dose/response studies for IL-2 (0-100 U/ml) alone and for fresh unstimulated PBL (0-10(5) cells/MTS) showed no effects on MTS growth. IL-2-activated PBL (0-10(5) cells/MTS), in contrast, modulated MTS growth in a multiphasic pattern: MTS growth was unperturbed for the first 3 days and then growth inhibition occurred, followed by MTS disintegration. Histological analysis showed that intact MTS histoarchitecture correlated with unperturbed growth, and increasing cell sloughing and MTS dissolution and replacement by activated PBL correlated with growth inhibition and disintegration. Flow-cytometric sorting of lymphocyte subset populations indicated that it was the Leu19+CD3- cells that produced these growth-modulatory effects. In contrast to the initial LAK cell resistance of MTS, single-cell suspensions demonstrated significant lysis in standard 4-h chromium-release assays. Differences between single cells and MTS suggest a potential for tissue-like organization as a factor in lymphokine-activated killing.

Safety and Tolerability of Single Intravenous Doses of T Cell Modulatory Peptide (TCMP‐80) in Healthy Volunteers

T Cell Modulatory Peptide (TCMP-80), L-lysine-L-serine, is a synthetic dipeptide structurally related to a selected amino acid sequence in human immunoglobulin G. Based on in vitro and preclinical in vivo testing, TCMP-80 has immunomodulatory properties. This report describes the first administration of TCMP-80 to man in a randomized, double-blind, placebo-controlled, single rising-dose tolerability trial. Healthy male volunteers received TCMP-80 or placebo as a 10-minute intravenous infusion. At weekly intervals, two of four subjects were given TCMP-80; the remaining two received placebo. Each subject could receive only one dose during the study. Dosing started at 0.01 mg/kg and was increased to 0.03, 0.1, 0.3, 1, 3, 6.5, and 10 mg/kg. CBCs, blood chemistries, urinalyses, and lymphocyte subset populations were monitored predose and postdose on Days 1, 5, and 14. Three placebo and three TCMP-80 subjects reported adverse events. Adverse events reported after TCMP-80 administration were mild in nature (headache, dizziness, hematoma at injection site), appeared to be independent of dose, and resolved without medical intervention. No clinically significant alterations in vital signs, physical examination parameters, or clinical laboratory values were observed. Based on the results of this study, TCMP-80 is safe and well-tolerated within the dose range studied when administered as single intravenous infusions. Additionally, this study design represents an approach to assess the safety of an investigational immunomodulatory drug.

Changes in lymphocyte subset distribution aid in the differential diagnosis of renal allograft dysfunction.

The distribution of selected lymphocyte subset populations in renal transplant patients was used to assist in the differential diagnosis of graft dysfunction. Patients experiencing dysfunction due to rejection showed consistent and significant decreases in relative numbers of CD 8 (cytotoxic/suppressor) lymphocytes. The ratio of CD 4 cells to CD 8 cells in this group of patients was generally greater than 2.00 due to decreases in CD 8 cells. Patients showing graft dysfunction due to viral infections showed consistent and significant increases in CD 8 cells which also bear the HNK-1 or the HLA-Dr determinants. Serial monitoring for these dual-marked lymphocytes on a weekly basis can be of considerable use in determining the etiology of graft dysfunction. Increases in other "activation" markers, including transferrin receptors, CD 38, and a T cell lineage specific activation antigen (TLiSA) were not specific for rejection; in fact, increases in CD38 were more often associated with viral infections. These studies indicated that lymphocyte subset determinations done on a regular basis can help distinguish graft dysfunction due to viral infections from other causes. The ability to distinguish rejection episodes from stable grafts is less obvious. Although the alterations in lymphocyte subset distribution are not entirely specific, they can distinguish viral infections from rejection.