T lymphocyte proliferative capacity and CD4+/CD8+ ratio in primiparous and pluriparous lactating cows

2008 ◽  
Vol 75 (4) ◽  
pp. 457-465 ◽  
Author(s):  
Jalil Mehrzad ◽  
Xin Zhao
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Dairy Cows ◽  
T Lymphocyte ◽  
Farm Animals ◽  
T Lymphocyte Subsets ◽  
Lactating Cows ◽  
Proliferation Capacity ◽  
First Time ◽  
Increased Susceptibility

T cells play a central role in specific immunity; their populations and phenotypes could be affected by number of lactation in high-yielding dairy cows. To investigate the effects of parity on the dynamics of T lymphocytes, lymphoproliferative capacity, T lymphocyte subsets and CD4+/CD8+ ratio were studied in peripheral blood of primiparous and pluriparous dairy cows during mid–late lactation. A non-radioactive technique was also adapted for a detailed lymphoproliferation assay. Compared with the primiparous cows, the pluriparous cows exhibited weaker lymphoproliferative activity, larger number of CD4+ cells and substantially greater CD4+/CD8+ ratio in their blood circulation. The increase of the CD4+/CD8+ ratio in the blood of pluriparous dairy cows was mainly due to the rise in the proportion of CD4+ cells and decline in the proportion of CD8+ cells. This increase of the CD4+/CD8+ ratio coincided with the decrease of mitogen-induced proliferation capacity of T lymphocytes. Of four lymphocyte divisions or generations during the lymphoproliferation assay, maximal lymphocyte proliferation capacity at generation 3 in primiparous cows was markedly greater than in pluriparous cows. With an alternatively safer, faster and more reproducible assay (compared with 3H-thymidine scintillation assay) we showed for the first time that aging in dairy cows leads to a decreased mitogen-induced lymphoproliferation and disturbed proportion between CD4+ and CD8+ T cells. This CD4+-CD8+ imbalance together with diminished lymphoproliferative capacity may lead to a weaker T cytotoxic-mediated immunity and increased susceptibility to infectious diseases in pluriparous lactating cows. Our study also emphasizes further application of the methods in farm animals.

Changes in L-Selectin Expression by T Lymphocytes after Extracorporeal Photochemotherapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1961-1961
Author(s):  
Manuel Ramirez ◽  
Marta Gonzalez-Vicent ◽  
Antonio Perez-Martinez ◽  
Julian Sevilla ◽  
Luis Madero ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Receptor Activation ◽  
P Value ◽  
T Lymphocyte Subsets ◽  
Extracorporeal Photochemotherapy ◽  
Steroid Refractory

Abstract Extracorporeal photochemotherapy (ECP) is an emerging treatment modality for steroid-refractory acute and chronic graft versus host disease (GVHD). The mechanisms by which ECP works are still not fully understood, and modulation of dendritic cell subpopulations, a shift of cytokine profile from Th1 to Th2 and an increase of T-cell regulatory (Treg) cells have been related to the ECP beneficial effect. Changes on T-lymphocyte subsets other than Treg have been reported after ECP (Biol Blood Marrow Transplant2006; 12(1 Suppl 2):22–30.). We analyzed the effect of ECP on the T lymphocyte subsets of sixteen children receiving this form of therapy. Steroid refractory GVHD was defined as failure to respond to 2 mg/Kg/day of methylprednisolone after 5 days (acute GVHD) or failure to respond to steroids or flare of disease activity upon tapering (chronic GVHD). ECP was performed by an alternative approach to that of the classical UVAR XTS system. This alternative method is based on a continuous-flow cell separator (COBE Spectra) that allow to process more mononuclear cells in a smaller volume and it is less time-consuming, both important advantages for pediatric patients. We studied the L-selectin (CD62L) and the CD45RA expression on CD4 and CD8 lymphocytes by flow cytometry. This combination allowed us to distinguish naive (TN, CD62L+CD45RA+), central memory (TCM, CD62L+CD45RA+), effector memory (TEM, CD62L+CD45RA+), and terminal differentiated T cells (TT, CD62L+CD45RA+), as described in Science2000;290:92–97. We compared the proportion of each of these four subpopulations, as well as the L-selectin positive and L-selectin negative ones, in samples collected from peripheral blood before the first (PRE) and after the last (POST) ECP procedures. Statistical analyses were done by the Wilcoxon signed-rank test. Results are shown in the following tables: CD4 SUBSETS & ECP PRE POST p value TN 6.58 ± 2.39 6.18 ± 2.96 0.2003 TCM 58.17 ± 4.49 43.85 ± 4.78 0.0268 TEM 34.64 ± 4.51 46.86 ± 4.89 0.0356 TT 0.6 ± 0.18 3.11 ± 1.46 0.1704 CD62Lpos 64.76 ± 4.4 50.03 ± 5.45 0.0268 CD62Lneg 35.23 ± 4.4 49.97 ± 5.45 0.0268 CD8 SUBSETS & ECP PRE POST p value TN 16.95 ± 3.94 12.53 ± 4.05 0.2343 TCM 28.8 ± 4.95 12.27 ± 2.86 0.0013 TEM 46.62 ± 5.79 51.4 ± 4.22 0.1477 TT 11.17 ± 3.34 23.52 ± 4.79 0.0105 CD62Lpos 45.75 ± 6.1 24.8 ± 5.34 0.0174 CD62Lneg 53.8 ± 6.07 74.92 ± 5.31 0.0174 The clinical outcome of the patients was always positive, with more than 50% achieving complete remission. The proportion of L-selectin expressing T lymphocytes significantly diminished after ECP, both in CD4 and in CD8 cells. The reason for these changes are currently unknown. L-selectin is an important T-cell homing receptor for T-cell entry into lymph nodes via high endothelial venules. Expression of CD62L is rapidly lost following T-cell receptor activation, leading to exit from the lymph node into the periphery and sites of inflammation. CD62Lneg and CD62Lpos also differ in their functional abilities, such as cytokine secretion and cytolytic potential. Our results suggest that ECP may have an impact in the trafficking patterns of T lymphocytes, redirectioning T cells from lymphoid to extralymphoid organs. In addition, ECP was associated to a redistribution of the pool of non-naive T lymphocytes.

scholarly journals Flow cytometric analysis of T lymphocytes and cytokines in aqueous humor of patients with varicella zoster virus-mediated acute retinal necrosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao Kang ◽  
Yunbo Wei ◽  
Ming Liu ◽  
Di Yu ◽  
Yong Tao
Keyword(s):  
T Lymphocytes ◽  
Varicella Zoster Virus ◽  
Aqueous Humor ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Flow Cytometric Analysis ◽  
T Lymphocyte Subsets ◽  
Varicella Zoster ◽  
Flow Cytometric ◽  
Cd8 T Lymphocytes

Abstract Background The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder. Methods Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed. Results VZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = − 0.834). Conclusion The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

scholarly journals Increased Frequency of Regulatory T Cells and T Lymphocyte Activation in Persons with Previously Treated Extrapulmonary Tuberculosis

2011 ◽  
Vol 19 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Alexandre S. de Almeida ◽  
Christina T. Fiske ◽  
Timothy R. Sterling ◽  
Spyros A. Kalams
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Pulmonary Tuberculosis ◽  
Treg Cell ◽  
T Lymphocyte ◽  
Extrapulmonary Tuberculosis ◽  
Lymphocyte Activation ◽  
Content Type ◽  
T Lymphocyte Activation ◽  
Previously Treated

ABSTRACTExtrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+T lymphocytes in general, are important in the host immune response toMycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions beforeM. tuberculosisinfection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts withM. tuberculosisinfection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+CD25hiCD127lowFoxP3+cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls withM. tuberculosisinfection, and 18 controls withoutM. tuberculosisinfection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.20%) (P= 0.001). The median proportion of CD4+T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.32%) (P= 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis.

scholarly journals Assessment of the Percentages of T-lymphocyte Subsets in the Peripheral Blood of Mediterranean Spotted Fever Patients

2020 ◽  
Vol 18 (2) ◽  
pp. 111-119
Author(s):  
Iv. Baltadzhiev ◽  
P. Pavlov
Keyword(s):  
T Cells ◽  
Disease Severity ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Spotted Fever ◽  
Healing Process ◽  
Cell Subset ◽  
Rickettsia Conorii ◽  
Mediterranean Spotted Fever ◽  
T Lymphocyte Subsets

Purpose: Mediterranean spotted fever (MSF) is a rickettsial disease. The aim was to evaluate the host immunе response to Rickettsia conorii. Material and methods: 62 patients were assigned into three groups: with mild, moderate or severe clinical forms of MSF. Controls were 32 healthy individuals. The diagnosis of MSF was confirmed by the indirect immunofluorescence assay. Immunophenotyping was performed using Epics XL-MCL Coulter. Results: The percentage of immune competent (CD3+) cells decreased, whereas that of helper/inducer (CD3+CD4+) and suppressor/cytotoxic (CD3+CD8+) did not change compared to controls. All three T-cell subset percentages did not parallel the disease severity. Naïve T-cells (CD4+CD45RA+) showed reduced levels, whereas activated memory (CD4+CD45RO+) T-cells did not change significantly. The percentage of activated (CD3+HLA-DR+) T-cells increased regardless of the disease severity, till the rise of stimulatory molecules (CD38+total) matched the disease severity forms. The percentage of costimulatory CD28-molecules corresponded to the disease severity as their levels increased significantly in mild forms and showed an evident downward trend towards the severe ones. Conclusion: Reduced T-lymphocyte subsets are likely related to trans-migration into perivascular inflammatory foci. The increased percentage of T-lymphocytes armed with stimulatory molecules probably reflects the mobilization of cell-mediated immune response in the healing process.

Flow Cytometric Analysis of T Lymphocytes and Cytokines in Aqueous Humor of Patients with Varicella Zoster Virus-mediated Acute Retinal Necrosis

2020 ◽  
Author(s):  
Hao Kang ◽  
Yunbo Wei ◽  
Ming Liu ◽  
Di Yu ◽  
Yong Tao
Keyword(s):  
T Lymphocytes ◽  
Varicella Zoster Virus ◽  
Aqueous Humor ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Flow Cytometric Analysis ◽  
T Lymphocyte Subsets ◽  
Varicella Zoster ◽  
Flow Cytometric ◽  
Cd8 T Lymphocytes

Abstract Background: The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder.Methods: Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-viral infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed.Results: VZV DNA was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p=0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8+CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p=0.006; p=0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4+CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p=0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p=0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p=0.009, r=0.92; p=0.039, r=-0.834).Conclusion: The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-viral infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

Association between gut microbiome and T lymphocytes among different primary tumor sites of patients with metastatic colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16013-e16013
Author(s):  
Lingyun Sun ◽  
Yunzi Yan ◽  
Dongmei Chen ◽  
Jun J. Mao ◽  
Yufei Yang
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Primary Tumor ◽  
Principal Component ◽  
Alpha Diversity ◽  
T Lymphocyte Subsets ◽  
Cell Immunity ◽  
Xiyuan Hospital

e16013 Background: Different primary tumor sites could impact colorectal cancer (CRC)’s survival outcomes and treatment effects. Previous studies had found that gut micro-biome distributions were different between left and right colon cancer(LCC, RCC). Out study aimed to further investigate the association between micro-biome and T lymphocytes among different tumor sites of patients with metastatic CRC. Methods: Between April 2018 and Mars 2019, we enrolled 40 metastatic CRC patients in Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China. We collected patients’ stool samples for micro-biome analysis by 16s rRNA sequencing approaches, as well as patients’ blood samples to analyses T lymphocyte subsets by flow cytometry methods. The study had been proved by ethics committee of Xiyuan Hospital (2016XLA122-1). All patients consented before enrollment. Results: Among 40 patients, 28% were female, with average age of 63±15 years old. There were 10 RCC, 9 LCC and 21 rectal cancer(RC) patients. Alpha diversity analysis showed that sobs index of the micro-biome of patients with RC and RC was significantly higher than whom were RCC(254.89±99, 247±89 versus.[vs.]101.17±51, p= 0.001). PCoA analysis on OTU level detected that first principal component[PC1] (26.24%) could be separated significantly between RCC and LCC( p= 0.048), as well as between RC and RCC (PC1,14.17%, p= 0.024). Community analysis showed that the proportion of Bacteroidetes was significantly higher in patients with RCC than whom with LCC and RC( p= 0.009). Conversely, the proportion of Firmicutes, Proteobacteria and Verrucomicrobia were higher in LCC patients than others( p= 0.37, 0.047 and 0.032 respectively). Canonical Correlation Analysis (CCA) analysis proved that the CD4+ and CD8+ T cells counts were environmental factors, which were significantly associated with certain micro-biome and samples from different tumor sites( p= 0.037 and 0.01 respectively). Trends showed that CD4+ T cells were positively related with samples of RC and bacteria parabacteroides and bifidobacterium, while CD8+ T cells were positively related with samples of RCC and bacteria Lachnospira, Sutterella and Bacteroides. Conclusions: In our study, we found that patients with LCC and RC had more beneficial gut micro-biome than whom with RCC. In addition, such difference might be associated with body T cell immunity.

High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects

2007 ◽  
Vol 103 (1) ◽  
pp. 396-401 ◽  
Author(s):  
Richard J. Simpson ◽  
Geraint D. Florida-James ◽  
Cormac Cosgrove ◽  
Greg P. Whyte ◽  
Scott Macrae ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
High Intensity ◽  
Clonal Expansion ◽  
High Intensity Exercise ◽  
Antigenic Stimulation ◽  
Blood Compartment ◽  
Senescent Phenotype

Clonal expansion of T lymphocytes in response to antigenic stimulation is a fundamental process of adaptive immunity. As a consequence of clonal expansion, some T lymphocytes acquire a senescent phenotype, fail to replicate in response to further antigenic stimulation, and express the killer cell lectin-like receptor G1 (KLRG1) and/or CD57. Physical exercise elicits a mobilization of large numbers of T lymphocytes into the bloodstream from peripheral lymphoid compartments, but the frequency of senescent cells in the mobilized population is not known. Eight male runners (age: 29 ± 9 yr; maximal O2 uptake 62 ± 6 ml·kg−1·min−1) performed an intensive treadmill-running protocol at 80% maximal O2 uptake to volitional exhaustion. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry. The percentage of all CD3+ T lymphocytes expressing KLRG1 and CD57 increased with exercise ( P < 0.01). The change in T-lymphocyte KLRG1 expression was attributed to both CD4+ and CD8 bright T cells, with the relative change being greater for the CD8 bright population ( P < 0.01). Mobilized T-lymphocyte populations expressing KLRG1 and CD57 appeared to extravasate the peripheral blood compartment after 1 h of recovery. In conclusion, T lymphocytes with a senescent phenotype are mobilized and subsequently removed from the bloodstream in response to acute high-intensity exercise. This suggests that T lymphocytes contained within the peripheral lymphoid compartments that are mobilized by exercise are likely to be at a more advanced stage of biological aging and have a reduced capacity for clonal expansion than blood-resident T cells.

scholarly journals Quantification of B cells and T lymphocyte subsets in bovine leukemia virus infected dairy cows

2012 ◽  
Vol 33 (4) ◽  
pp. 1487-1494 ◽  
Author(s):  
Alice Maria M P D Libera ◽  
Maiara Garcia Blagitz ◽  
Camila Freitas Batista ◽  
Andreia Oliveira Latorre ◽  
Claudia Regina Stricagnolo ◽  
...  
Keyword(s):  
B Cells ◽  
Dairy Cows ◽  
T Lymphocyte ◽  
Bovine Leukemia Virus ◽  
Lymphocyte Subsets ◽  
Leukemia Virus ◽  
T Lymphocyte Subsets

scholarly journals Protein Kinase B Regulates T Lymphocyte Survival, Nuclear Factor κb Activation, and Bcl-XL Levels in Vivo

2000 ◽  
Vol 191 (10) ◽  
pp. 1721-1734 ◽  
Author(s):  
Russell G. Jones ◽  
Michael Parsons ◽  
Madeleine Bonnard ◽  
Vera S.F. Chan ◽  
Wen-Chen Yeh ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Protein Kinase B ◽  
Active Form ◽  
Nuclear Factor ◽  
Clonal Deletion ◽  
Lymphocyte Survival

The serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4+CD8+ double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I–restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen–specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-XL. In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-κB activation via accelerated degradation of the NF-κB inhibitory protein IκBα. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-XL, and NF-κB) in vivo in T lymphocytes.

scholarly journals FUNCTION OF MACROPHAGES IN ANTIGEN RECOGNITION BY GUINEA PIG T LYMPHOCYTES

1973 ◽  
Vol 138 (5) ◽  
pp. 1213-1229 ◽  
Author(s):  
Ethan M. Shevach ◽  
Alan S. Rosenthal
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Lymphocytes ◽  
Binding Site ◽  
T Lymphocyte ◽  
Lymphocyte Transformation ◽  
Antigen Recognition ◽  
Histocompatibility Antigens ◽  
Recognition Sites

A number of recent studies have suggested that the main functional role of the product of the immune response (Ir) genes is in the process of antigen recognition by the T lymphocyte. The observation in the accompanying report that the interaction of macrophage-associated antigen with immune T lymphocytes requires that both cells share histocompatibility antigens raised the question as to whether the macrophage played a role in the genetic control of the immune response or even if the macrophage were the primary cell in which the product of the Ir gene is expressed. In the current study, parental macrophages were pulsed with an antigen, the response to which is controlled by an Ir gene lacking in that parent; these macrophages were then mixed with T cells derived from the (nonresponder x responder)F1 and the resultant stimulation was measured. No stimulation was seen when column-purified F1 lymph node lymphocytes were mixed with antigen-pulsed macrophages from the nonresponder parent. However, when the highly reactive peritoneal exudate lymphocyte population was used as the indicator cells, parental macrophages pulsed with an antigen whose Ir gene they lacked were capable of initiating F1 T-cell proliferation. The magnitude of stimulation was approximately 1/10 that seen when macrophages from either the responder parent or the F1 were used. In order to explain this observation, we hypothesize that antigen recognition sites on the T lymphocyte are physically related to a macrophage-binding site and both are linked to the serologically determined histocompatibility antigens. Thus, parental macrophages pulsed with an antigen, whose Ir gene they lack, activate F1 cells poorly because the recognition sites for the antigen are physically related to the macrophage-binding site of the responder parent while the main contacts between the cells are at the nonresponder binding sites. Experiments performed with alloantisera lend support to this hypothesis. Thus, when parental macrophages are pulsed with any antigen and added to F1 T cells, an alloantiserum directed against parental histocompatibility antigens reacts with both the lymphocyte and the macrophage and thereby inhibits macrophage-lymphocyte interaction and abolishes antigen-induced lymphocyte transformation. When the alloantisera are directed at determinants present solely on the T lymphocyte, they only inhibit the recognition of antigens controlled by the Ir gene linked to the histocompatibility antigen against which they are directed. We conclude from these studies that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.

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