Cancer Immunology

2015 ◽  
Author(s):  
Clifford S. Cho ◽  
Amanda Contreras
Keyword(s):  
Immune System ◽  
T Cell ◽  
Cell Function ◽  
Cytotoxic T Lymphocyte ◽  
Continuous Process ◽  
Effective Means ◽  
Full Complement ◽  
Activated T Cell ◽  
Antigen Presenting ◽  
Cell Inhibition

The immune system conducts a continuous process of immunologic surveillance for new cancer cells that is likely capable of eradicating many potential malignancies before they become clinically evident. Nascent tumors can, however, use escape mechanisms to avoid this control. It is hoped that therapeutic manipulation of this balance between cancer and host may allow us to harness the immune system as an effective means of treating established tumors. This review summarizes the immunologic response, immunoediting, and clinical strategies in cancer immunotherapy. Figures show activation of CD8+ cytotoxic T lymphocytes and CD4+ T helper cells by an antigen-presenting cell; inhibition of T cells specific for an antigen being presented in the absence of a full complement of costimulatory interactions, as might be present on an immature dendritic cell, engagement of cytotoxic T lymphocyte–associated protein 4 by B7, which serves to downregulate T cell function, and downregulation of major histocompatibility proteins on the surfaces of tumor cells; and the kinetics of activated T cell homeostasis in the presence of cancer. This review contains 3 figures and 39 references.

scholarly journals Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function.

1985 ◽  
Vol 161 (5) ◽  
pp. 1029-1047 ◽  
Author(s):  
A M Kruisbeek ◽  
J J Mond ◽  
B J Fowlkes ◽  
J A Carmen ◽  
S Bridges ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cell Function ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Class Ii ◽  
Antibody Treatment ◽  
Cell Functions ◽  
Antigen Presenting

In an effort to elucidate the role of intrathymic Ia-bearing antigen-presenting cells (APC) on the development of the class II-restricted T cell repertoire, we examined the effect of neonatal anti-I-A treatment on both intrathymic and splenic APC function; on the generation of Lyt-2-,L3T4+, Lyt-2+,L3T4-, and Lyt-2+,L3T4+ T cells; and on the development of class I- and class II-specific T cell functions. Both the thymus and the spleen are completely devoid of Lyt-2-,L3T4+ T cells in young mice treated from birth with anti-I-A, and also lack functions associated with this subset, i.e., alloantigen-specific interleukin 2 production (present report), allo-class II-specific and self-class II-restricted T cell proliferative responses, and helper cell function for the generation of cytotoxic T lymphocyte responses (18). Development of the Lyt-2+,L3T4- subset proceeds undisturbed in these mice, in accord with the previously reported normal levels of cytotoxic T lymphocyte precursors (18). The thymus contains normal numbers of the immature cortical Lyt-2+,L3T4+ cells, indicating that acquisition of the L3T4 marker, in and of itself, is not influenced by anti-I-A treatment. This striking absence of the lineage of T cells responsible for class II-specific T cell functions is correlated with absence of thymic APC function for class II-restricted T cell clones. When anti-I-A-treated mice are allowed to recover from the antibody treatment, splenic and thymic APC function return to normal in 2-3 wk, and thymic Lyt-2-,L3T4+ T cell numbers and functions reappear before such cells are detectable in the spleen. Collectively, these findings suggest that development of the Lyt-2-,L3T4+ lineage of class II-specific T cells is entirely dependent on functional I-A-bearing APC cells in the thymus. In addition, the presence of normal levels of Lyt-2+,L3T4-T cells argues that generation of the two major subsets of T cells (i.e., Lyt-2+,L3T4- and Lyt-2-,L3T4+) occurs through separate events, involving unique sites of interactions between precursor T cells and nonlymphoid major histocompatibility complex-bearing thymus cells.

scholarly journals Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 813
Author(s):  
Norwin Kubick ◽  
Pavel Klimovich ◽  
Patrick Henckell Flournoy ◽  
Irmina Bieńkowska ◽  
Marzena Łazarczyk ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Positive Selection ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Single Gene ◽  
Ancestral Reconstruction ◽  
Critical Function ◽  
Interleukin Receptors

Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have emerged during the divergence of jawed vertebrates. However, little is known about the evolution of interleukins and their origin. We traced the evolution of interleukins and their receptors from Placozoa to primates. We performed phylogenetic analysis, ancestral reconstruction, HH search, and positive selection analysis. Our results indicated that various interleukins' emergence predated CD4+ T cells divergence. IL14 was the most ancient interleukin with homologs in fungi. Invertebrates also expressed various interleukins such as IL41 and IL16. Several interleukin receptors also appeared before CD4+ T cells divergence. Interestingly IL17RA and IL17RD, which are known to play a fundamental role in Th17 CD4+ T cells first appeared in mollusks. Furthermore, our investigations showed that there is not any single gene family that could be the parent group of interleukins. We postulate that several groups have diverged from older existing cytokines such as IL4 from TGFβ, IL10 from IFN, and IL28 from BCAM. Interleukin receptors were less divergent than interleukins. We found that IL1R, IL7R might have diverged from a common invertebrate protein that contained TIR domains, conversely, IL2R, IL4R and IL6R might have emerged from a common invertebrate ancestor that possessed a fibronectin domain. IL8R seems to be a GPCR that belongs to the rhodopsin-like family and it has diverged from the Somatostatin group. Interestingly, several interleukins that are known to perform a critical function for CD4+ T cells such as IL6, IL17, and IL1B have gained new functions and evolved under positive selection. Overall evolution of interleukin receptors was not under significant positive selection. Interestingly, eight interleukin families appeared in lampreys, however, only two of them (IL17B, IL17E) evolved under positive selection. This observation indicates that although lampreys have a unique adaptive immune system that lacks CD4+ T cells, they could be utilizing interleukins in homologous mode to that of the vertebrates' immune system. Overall our study highlights the evolutionary heterogeneity within the interleukins and their receptor superfamilies and thus does not support the theory that interleukins evolved solely in jawed vertebrates to support T cell function. Conversely, some of the members are likely to play conserved functions in the innate immune system.

scholarly journals CERI, CEFX, and CPI: Largely Improved Positive Controls for Testing Antigen-Specific T Cell Function in PBMC Compared to CEF

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 248
Author(s):  
Alexander A. Lehmann ◽  
Pedro A. Reche ◽  
Ting Zhang ◽  
Maneewan Suwansaard ◽  
Paul V. Lehmann
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Racial Bias ◽  
Immune Monitoring ◽  
Functional Fitness ◽  
Peripheral Blood Mononuclear ◽  
Cell Immunity ◽  
Antigen Presenting ◽  
Positive Controls

Monitoring antigen-specific T cell immunity relies on functional tests that require T cells and antigen presenting cells to be uncompromised. Drawing of blood, its storage and shipment from the clinical site to the test laboratory, and the subsequent isolation, cryopreservation and thawing of peripheral blood mononuclear cells (PBMCs) before the actual test is performed can introduce numerous variables that may jeopardize the results. Therefore, no T cell test is valid without assessing the functional fitness of the PBMC being utilized. This can only be accomplished through the inclusion of positive controls that actually evaluate the performance of the antigen-specific T cell and antigen presenting cell (APC) compartments. For Caucasians, CEF peptides have been commonly used to this extent. Moreover, CEF peptides only measure CD8 cell functionality. We introduce here universal CD8+ T cell positive controls without any racial bias, as well as positive controls for the CD4+ T cell and APC compartments. In summary, we offer new tools and strategies for the assessment of PBMC functional fitness required for reliable T cell immune monitoring.

scholarly journals CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance

2009 ◽  
Vol 206 (2) ◽  
pp. 421-434 ◽  
Author(s):  
Randall H. Friedline ◽  
David S. Brown ◽  
Hai Nguyen ◽  
Hardy Kornfeld ◽  
JinHee Lee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Cytotoxic T Lymphocyte ◽  
Critical Role ◽  
Lymphoproliferative Disease ◽  
In Trans ◽  
And Function

Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3+ regulatory T cells. CTLA-4–deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4–deficient and –sufficient bone marrow (BM)–derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4−/− T cells in trans by CTLA-4–sufficient T cells is a reversible process that requires the persistent presence of FOXP3+ regulatory T cells with a diverse TCR repertoire. Based on gene expression studies, the regulatory T cells do not appear to act directly on T cells, suggesting they may instead modulate the stimulatory activities of antigen-presenting cells. These results demonstrate that CTLA-4 is absolutely required for FOXP3+ regulatory T cell function in vivo.

scholarly journals CD8β Increases CD8 Coreceptor Function and Participation in TCR–Ligand Binding

1996 ◽  
Vol 184 (6) ◽  
pp. 2439-2444 ◽  
Author(s):  
Valery Renard ◽  
Pedro Romero ◽  
Eric Vivier ◽  
Bernard Malissen ◽  
Immanuel F. Luescher
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
Cell Function ◽  
Cytotoxic T Lymphocyte ◽  
Photoaffinity Labeling ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Β Cells ◽  
Cd8 Cells ◽  
Peptide Derivative

To study the role of CD8β in T cell function, we derived a CD8α/β− (CD8−/−) T cell hybridoma of the H-2Kd–restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8α alone or together with CD8β. All three hybridomas released interleukin 2 upon incubation with L cells expressing Kd–peptide derivative complexes, though CD8α/β cells did so more efficiently than CD8α/α and especially CD8−/− cells. More strikingly, only CD8α/β cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab′ fragments of the anti-Kd α3 monoclonal antibody SF11.1.1 or substitution of Kd D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR–ligand binding on CD8α/β cells was ∼5- and 20-fold more avid than on CD8α/a and CD8−/− cells, respectively. SF1-1.1.1 Fab′ or Kd mutation D227K reduced the TCR photoaffinity labeling on CD8α/β cells to approximately the same low levels observed on CD8−/− cells. These results indicate that CD8α/β is a more efficient coreceptor than CD8α/α, because it more avidly strengthens TCR–ligand binding.

Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo

10.1038/nm962 ◽  
2003 ◽  
Vol 9 (12) ◽  
pp. 1469-1476 ◽  
Author(s):  
Douglas G Millar ◽  
Kristine M Garza ◽  
Bernhard Odermatt ◽  
Alisha R Elford ◽  
Nobuyuki Ono ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Antigen Presenting Cell ◽  
Antigen Presenting

scholarly journals Deficiency in NOD Antigen-Presenting Cell Function May Be Responsible for Suboptimal CD4+CD25+ T-Cell-Mediated Regulation and Type 1 Diabetes Development in NOD Mice

Diabetes ◽  
2006 ◽  
Vol 55 (7) ◽  
pp. 2098-2105 ◽  
Author(s):  
P. Alard ◽  
J. N. Manirarora ◽  
S. A. Parnell ◽  
J. L. Hudkins ◽  
S. L. Clark ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Cell Function ◽  
Nod Mice ◽  
Antigen Presenting Cell ◽  
Diabetes Development ◽  
Antigen Presenting

scholarly journals Counteraction of HLA-C-Mediated Immune Control of HIV-1 by Nef

2010 ◽  
Vol 84 (14) ◽  
pp. 7300-7311 ◽  
Author(s):  
Anke Specht ◽  
Amalio Telenti ◽  
Raquel Martinez ◽  
Jacques Fellay ◽  
Elizabeth Bailes ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Function ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Immune Control ◽  
Viral Loads ◽  
Mhc Ii ◽  
High Set ◽  
Antigen Presenting ◽  
Hiv 1

ABSTRACT A host genetic variant (−35C/T) correlates with increased human leukocyte antigen C (HLA-C) expression and improved control of HIV-1. HLA-C-mediated immunity may be particularly protective because HIV-1 is unable to remove HLA-C from the cell surface, whereas it can avoid HLA-A- and HLA-B-mediated immunity by Nef-mediated down-modulation. However, some individuals with the protective −35CC genotype exhibit high viral loads. Here, we investigated whether the ability of HIV-1 to replicate efficiently in the “protective” high-HLA-C-expression host environment correlates with specific functional properties of Nef. We found that high set point viral loads (sVLs) were not associated with the emergence of Nef variants that had acquired the ability to down-modulate HLA-C or were more effective in removing HLA-A and HLA-B from the cell surface. However, in individuals with the protective −35CC genotype we found a significant association between sVLs and the efficiency of Nef-mediated enhancement of virion infectivity and modulation of CD4, CD28, and the major histocompatibility complex class II (MHC-II)-associated invariant chain (Ii), while this was not observed in subjects with the −35TT genotype. Since the latter Nef functions all influence the stimulation of CD4+ T helper cells by antigen-presenting cells, they may cooperate to affect both the activation status of infected T cells and the generation of an antiviral cytotoxic T-lymphocyte (CTL) response. In comparison, different levels of viremia in individuals with the common −35TT genotype were not associated with differences in Nef function but with differences in HLA-C mRNA expression levels. Thus, while high HLA-C expression may generally facilitate control of HIV-1, Nef may counteract HLA-C-mediated immune control in some individuals indirectly, by manipulating T-cell function and MHC-II antigen presentation.

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