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1.
Bettahi I Dasgupta G Renaudet O Chentoufi AA Zhang X Carpenter D Yoon S Dumy P BenMohamed L 《Cancer immunology, immunotherapy : CII》2009,58(2):187-200
Molecularly defined synthetic vaccines capable of inducing both antibodies and cellular anti-tumor immune responses, in a
manner compatible with human delivery, are limited. Few molecules achieve this target without utilizing external immuno-adjuvants.
In this study, we explored a self-adjuvanting glyco-lipopeptide (GLP) as a platform for cancer vaccines using as a model MO5,
an OVA-expressing mouse B16 melanoma. A prototype B and T cell epitope-based GLP molecule was constructed by synthesizing
a chimeric peptide made of a CD8+ T cell epitope, from ovalbumin (OVA257–264) and an universal CD4+ T helper (Th) epitope (PADRE). The resulting CTL–Th peptide backbones was coupled to a carbohydrate B cell epitope based
on a regioselectively addressable functionalized templates (RAFT), made of four α-GalNAc molecules at C-terminal. The N terminus
of the resulting glycopeptides (GP) was then linked to a palmitic acid moiety (PAM), obviating the need for potentially toxic
external immuno-adjuvants. The final prototype OVA-GLP molecule, delivered in adjuvant-free PBS, in mice induced: (1) robust
RAFT-specific IgG/IgM that recognized tumor cell lines; (2) local and systemic OVA257–264-specific IFN-γ producing CD8+ T cells; (3) PADRE-specific CD4+ T cells; (4) OVA-GLP vaccination elicited a reduction of tumor size in mice inoculated with syngeneic murine MO5 carcinoma
cells and a protection from lethal carcinoma cell challenge; (5) finally, OVA-GLP immunization significantly inhibited the
growth of pre-established MO5 tumors. Our results suggest self-adjuvanting glyco-lipopeptide molecules as a platform for B
Cell, CD4+, and CD8+ T cell epitopes-based immunotherapeutic cancer vaccines.
Both I. Bettahi and G. Dasgupta have contributed equally to this work. 相似文献
2.
Elkord E Burt DJ Drijfhout JW Hawkins RE Stern PL 《Cancer immunology, immunotherapy : CII》2008,57(6):833-847
Background The human 5T4 (h5T4) oncofoetal antigen is expressed by a wide variety of human carcinomas including colorectal, ovarian,
gastric and renal, but rarely on normal tissues. Its restricted expression on tumour tissues as well as its association with
tumour progression and bad prognosis has driven the development of a MVA-based vaccine (TroVax) which has been tested in several
early phase clinical trials and these studies have led to the start of a phase III trial in renal cell carcinoma patients.
We have recently shown that CD8+ T cells recognizing h5T4 can be generated in the absence of CD4+ T cells from peripheral blood lymphocytes of human healthy individuals.
Results We report the existence and expansion of human CD4+ T cells against h5T4 by stimulation with autologous monocyte-derived dendritic cells infected with a replication defective
adenovirus encoding the h5T4 cDNA (Ad-h5T4). The h5T4-specific T-cell responses in normal individuals are enhanced by initial
depletion of CD25+ cells (putative T regulatory cells) prior to the in vitro stimulation. We have identified a novel h5T4-derived 15-mer peptide
recognized by CD4+ T cells in HLA-DR4 positive healthy individuals. Interestingly, CD4+ T cells spontaneously recognizing a different 5T4 epitope restricted by HLA-DR were identified in tumour-infiltrating lymphocytes
isolated from a regressing renal cell carcinoma lung metastasis.
Conclusion Our data show that CD4+ T cells recognizing h5T4 can be expanded and detected in healthy individuals and a renal cell carcinoma patient. Such h5T4-specific
CD4+ T cells boosted or induced by vaccination could act to modulate both cell or antibody mediated anti-tumour responses.
This work was supported by Cancer Research UK. 相似文献
3.
We have previously demonstrated that multiple immunizations with vector-based vaccines containing transgenes for tumor Ags
and a triad of costimulatory molecules (TRICOM) enhance the expansion and functional avidity of Ag-specific memory CD8+ T cells in a mouse model. However, the effect of enhanced costimulation on human memory CD8+ T cells is still unclear. The study reported here was an in vitro investigation of the proliferation and function of CEA-specific
human memory CD8+ T cells following enhanced costimulation. Our results demonstrated that TRICOM costimulation enhanced production of multiple
cytokines and expansion of CEA-specific memory CD8+ T cells. The lytic capacity of memory CTLs toward CEA+ tumors was also significantly enhanced. IL-2Rα (CD25) was upregulated dramatically following APC-TRICOM stimulation, suggesting
that the enhanced expansion of memory CD8+ T cells may be mediated by increased expression of IL-2R on memory T cells. The enhanced cytokine production and proliferation
following TRICOM signaling was completely blocked by the combination of neutralizing Abs against B7-1, ICAM-1, and LFA-3,
the costimulatory molecules comprising TRICOM. No difference in T-cell apoptosis was observed between APC-TRICOM and APC-wild-type
groups, as determined by annexin V, Bcl-2, and active caspase-3 staining. Results indicated that enhanced costimulation greatly
expanded human CEA-specific CD8+ T cells and enhanced T-cell function, without inducing increased apoptosis of CEA-specific memory CD8+ T cells. 相似文献
4.
Wölfl M Merker K Morbach H Van Gool SW Eyrich M Greenberg PD Schlegel PG 《Cancer immunology, immunotherapy : CII》2011,60(2):173-186
T cell-mediated immunotherapy against malignancies has been shown to be effective for certain types of cancer. However, ex vivo expansion of tumor-reactive T cells has been hindered by the low precursor frequency of such cells, often requiring multiple rounds of stimulation, resulting in full differentiation, loss of homing receptors and potential exhaustion of the expanded T cells. Here, we show that when using highly purified naïve CD8+ T cells, a single stimulation with peptide-pulsed, IFNγ/LPS-matured dendritic cells in combination with the sequential use of IL-21, IL-7 and IL-15 is sufficient for extensive expansion of antigen-specific T cells. Short-term expanded T cells were tumor-reactive, multifunctional and retained a central-memory-like phenotype (CD62L+, CCR7+, CD28+). The procedure is highly reproducible and robust as demonstrated for different healthy donors and for cancer patients. Such short-term tumor-antigen-primed, multifunctional T cells may therefore serve as a platform to target different malignancies accessible to immunotherapy. 相似文献
5.
Iero M Squarcina P Romero P Guillaume P Scarselli E Cerino R Carrabba M Toutirais O Parmiani G Rivoltini L 《Cancer immunology, immunotherapy : CII》2007,56(12):1979-1991
The use of “altered peptide ligands” (APL), epitopes designed for exerting increased immunogenicity as compared with native
determinants, represents nowadays one of the most utilized strategies for overcoming immune tolerance to self-antigens and
boosting anti-tumor T cell-mediated immune responses. However, the actual ability of APL-primed T cells to cross-recognize
natural epitopes expressed by tumor cells remains a crucial concern. In the present study, we show that CAP1-6D, a superagonist
analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly
promotes the generation of low-affinity CD8+ T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells. Short-term T cell cultures, obtained
by priming peripheral blood mononuclear cells from HLA-A*0201+ healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations
of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- γ release CEA+CRC cells. Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining
with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA
epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native
CAP1 peptide. Our data demonstrate that the efficient detection of self-antigen expressed by tumors could be a feature of
high avidity CD8-independent T cells, and underline the need for extensive analysis of tumor cross-recognition prior to any
clinical usage of APL as anti-cancer vaccines. 相似文献
6.
7.
Jinjong Myoung Hyun Seok Kang Wanqiu Hou Liping Meng Mauro C. Dal Canto Byung S. Kim 《Journal of virology》2012,86(24):13717-13728
Theiler''s virus-induced demyelinating disease has been extensively investigated as a model for persistent viral infection and multiple sclerosis (MS). However, the role of CD8+ T cells in the development of disease remains unclear. To assess the role of virus-specific CD8+ T cells in the pathogenesis of demyelinating disease, a single amino acid substitution was introduced into the predominant viral epitope (VP3 from residues 159 to 166 [VP3159-166]) and/or a subdominant viral epitope (VP3173-181) of susceptible SJL/J mice by site-directed mutagenesis. The resulting variant viruses (N160V, P179A, and N160V/P179A) failed to induce CD8+ T cell responses to the respective epitopes. Surprisingly, mice infected with N160V or N160V/P179A virus, which lacks CD8+ T cells against VP3159-166, did not develop demyelinating disease, in contrast to wild-type virus or P179A virus lacking VP3173-181-specific CD8+ T cells. Our findings clearly show that the presence of VP3159-166-specific CD8+ T cells, rather than viral persistence itself, is strongly correlated with disease development. VP3173-181-specific CD8+ T cells in the central nervous system (CNS) of these virus-infected mice expressed higher levels of transforming growth factor β, forkhead box P3, interleukin-22 (IL-22), and IL-17 mRNA but caused minimal cytotoxicity compared to that caused by VP3159-166-specific CD8+ T cells. VP3159-166-specific CD8+ T cells exhibited high functional avidity for gamma interferon production, whereas VP3173-181-specific CD8+ T cells showed low avidity. To our knowledge, this is the first report indicating that the induction of the IL-17-producing CD8+ T cell type is largely epitope specific and that this specificity apparently plays a differential role in the pathogenicity of virus-induced demyelinating disease. These results strongly advocate for the careful consideration of CD8+ T cell-mediated intervention of virus-induced inflammatory diseases. 相似文献
8.
9.
Albrecht J Frey M Teschner D Carbol A Theobald M Herr W Distler E 《Cancer immunology, immunotherapy : CII》2011,60(2):235-248
Clinical tumor remissions after adoptive T-cell therapy are frequently not durable due to limited survival and homing of transfused
tumor-reactive T cells, what can be mainly attributed to the long-term culture necessary for in vitro expansion. Here, we
introduce an approach allowing the reliable in vitro generation of leukemia-reactive cytotoxic T lymphocytes (CTLs) from naive
CD8+ T cells of healthy donors, leading to high cell numbers within a relatively short culture period. The protocol includes the
stimulation of purified CD45RA+ CD8+ T cells with primary acute myeloid leukemia blasts of patient origin in HLA-class I-matched allogeneic mixed lymphocyte-leukemia
cultures. The procedure allowed the isolation of a large diversity of HLA-A/-B/-C-restricted leukemia-reactive CTL clones
and oligoclonal lines. CTLs showed reactivity to either leukemia blasts exclusively, or to leukemia blasts as well as patient-derived
B lymphoblastoid-cell lines (LCLs). In contrast, LCLs of donor origin were not lysed. This reactivity pattern suggested that
CTLs recognized leukemia-associated antigens or hematopoietic minor histocompatibility antigens. Consistent with this hypothesis,
most CTLs did not react with patient-derived fibroblasts. The efficiency of the protocol could be further increased by addition
of interleukin-21 during primary in vitro stimulation. Most importantly, leukemia-reactive CTLs retained the expression of
early T-cell differentiation markers CD27, CD28, CD62L and CD127 for several weeks during culture. The effective in vitro
expansion of leukemia-reactive CD8+ CTLs from naive CD45RA+ precursors of healthy donors can accelerate the molecular definition of candidate leukemia antigens and might be of potential
use for the development of adoptive CTL therapy in leukemia. 相似文献
10.
Maarten L. Zandvliet Ellis van Liempt Inge Jedema Louise A. Veltrop-Duits Roel Willemze Henk-Jan Guchelaar J. H. Frederik Falkenburg Pauline Meij 《Cytotherapy》2010,12(7):933-944
Background aimsAdoptive transfer of cytomegalovirus (CMV)-specific memory T cells can be used for treatment of CMV reactivation after allogeneic stem cell transplantation. As co-ordinated CD8+ and CD4+ T cells specific for a broad repertoire of CMV epitopes may be most effective for adoptive immunotherapy, the aim of this study was to isolate these cells from peripheral blood of CMV seropositive donors, irrespective of their HLA type.MethodsActivation of CMV-specific CD8+ and CD4+ T cells was compared after stimulation of donor peripheral blood with minimal epitope peptides, pools of overlapping 15-mer peptides or full-length protein. Furthermore, the kinetics of interferon (IFN)-γ production after stimulation was analyzed to determine the optimal time-point for IFN-γ-based isolation of CMV-specific T cells. The specificity, phenotype and functionality of generated T-cell lines were analyzed.ResultsCMV protein-spanning 15-mer peptide pools induced simultaneous activation of both CD8+ and CD4+ CMV-specific T cells, while full-length CMV protein only efficiently activated CD4+ CMV-specific T cells. Isolation of IFN-γ-secreting cells at the peak of the IFN-γ response after 4-h stimulation with CMV pp65 and IE1 peptide pools resulted in efficient enrichment of CMV-specific T cells. The T-cell lines contained high frequencies of CD8+ and CD4+ T cells recognizing multiple CMV pp65 and IE1 epitopes, and produced IFN-γ and tumor necrosis factor (TNF)-α upon specific restimulation.ConclusionsThis study provides a feasible strategy for the rapid generation of clinical-grade CD8+ and CD4+ T-cell lines with high specificity for multiple CMV pp65 and IE1 epitopes, which may be used for effective adoptive immunotherapy. 相似文献
11.
CD4+CD25+Foxp3+ regulatory T (Treg) cells are believed to play an important role in suppressing autoimmunity and maintaining peripheral tolerance. How their survival is regulated in the periphery is less clear. Here we show that Treg cells express receptors for gamma chain cytokines and are dependent on an exogenous supply of these cytokines to overcome cytokine withdrawal apoptosis in vitro. This result was validated in vivo by the accumulation of Treg cells in Bim-/- and Bcl-2 tg mice which have arrested cytokine deprivation apoptosis. We also found that CD25 and Foxp3 expression were down-regulated in the absence of these cytokines. CD25+ cells from Scurfy mice do not depend on cytokines for survival demonstrating that Foxp3 increases their dependence on cytokines by suppressing cytokine production in Treg cells. Our study reveals that the survival of Treg cells is strictly dependent on cytokines and cytokine producing cells because they do not produce cytokines. Our study thus, demonstrates that different gamma chain cytokines regulate Treg homeostasis in the periphery by differentially regulating survival and proliferation. These findings may shed light on ways to manipulate Treg cells that could be utilized for their therapeutic applications. 相似文献
12.
David A Horwitz 《Arthritis research & therapy》2010,12(1):101
Various abnormalities in CD4+CD25+ regulatory T cells (Tregs) in systemic lupus erythematosus (SLE) include increased Foxp3+ cells that are CD25 negative. Barring methodological technical factors, these cells could be atypical Tregs or activated
non-Treg CD4+ cells that express Foxp3. Two groups have reached opposite conclusions that could possibly reflect the subjects studied.
One group studied untreated new-onset SLE and suggested that these T cells were mostly CD25-Foxp3+ non-Tregs. The other group studied patients with long-standing disease and suggested that these cells are mostly dysfunctional
Tregs. A third group reported increased Foxp3+CD4+CD25dim rather than CD25- cells in active SLE and these were also non-Tregs. Thus, it is likely that not all Foxp3+ T cells in SLE have protective suppressive activity. 相似文献
13.
Petrovas C Mueller YM Yang G Altork SR Jacobson JM Pitsakis PG Mounzer KC Altman JD Katsikis PD 《Apoptosis : an international journal on programmed cell death》2007,12(12):2175-2186
We have recently provided data suggesting a potential role for mitochondria and Bcl-2-family molecules in apoptosis sensitivity
of HIV-specific CD8+ T cells. Here, we report on the role of filamentous (F) actin in this process. Disruption of actin by cytochalasin D (cytD)
or lantrunculin A remarkably reduced CD95/Fas-induced apoptosis of HIV-specific CD8+ T cells while their spontaneous apoptosis was unaffected. This inhibition cannot be attributed to changes of CD95/Fas distribution
or levels in these cells. Furthermore, cytD treatment reduced CD95/Fas-induced apoptosis of CD8+ T cells from HIV+ patients independently of their differentiation status. CD95/Fas-induced apoptosis of both CD38+ and CD38− HIV-specific CD8+ T cells was inhibited by cytD treatment indicating that actin mediates this apoptotic process independently of the activation
level of these cells. CytD was found to reduce the activation of caspase-8 induced by short treatment of purified CD8+ T cells from HIV+ patients with anti-CD95/Fas. Our data reveal actin as a critical mediator of HIV-specific CD8+ T cell apoptosis; further analysis of the molecular mechanisms governing this process may potentially contribute to design
new therapies targeting the enhancement of the immune system in HIV infection. 相似文献
14.
Bardos T Czipri M Vermes C Finnegan A Mikecz K Zhang J 《Arthritis research & therapy》2003,5(2):R106-R113
Accumulating evidence suggests that regulatory T cells play a crucial role in preventing autoimmunity. Recently, a naturally
occurring CD4+CD25+ T-cell subset that is anergic and also suppressive has been shown to suppress autoimmunity in several animal models. We used
proteoglycan-induced arthritis (PGIA) as a study model to investigate the role of the CD4+CD25+ regulatory T cells in autoimmune arthritis. There was no significant change in the percentage of CD4+CD25+ T cells during the immunization period when proteoglycan- or ovalbumin-immunized BALB/c and C57BL/6 mice were compared. An
adoptive transfer study showed that the CD4+CD25+ T cells did not protect severe combined immunodeficient mice from arthritis when they were cotransferred with splenocytes
from arthritic animals. Similarly, depletion of the CD4+CD25+ T cells did not enhance the onset of the disease or disease severity in severe combined immunodeficient mice. Moreover, CD28-deficient
mice, which have very few CD4+CD25+ T cells, were highly resistant to PGIA. These findings indicate that the CD4+CD25+ regulatory T cells may not play a critical role in controlling PGIA. 相似文献
15.
Duftner C Goldberger C Falkenbach A Würzner R Falkensammer B Pfeiffer KP Maerker-Hermann E Schirmer M 《Arthritis research & therapy》2003,5(5):R292-R300
Circulating CD3+CD4+CD28- cells exhibit reduced apoptosis and were found to be more enriched in patients with ankylosing spondylitis than in age-matched healthy control individuals (7.40 ± 6.6% versus 1.03 ± 1.0%; P < 0.001). Levels of CD4+CD28- T cells correlate with disease status as measured using a modified metrology score, but they are independent of age and duration of ankylosing spondylitis. CD4+CD28- T cells produce IFN-γ and perforin, and thus they must be considered proinflammatory and cytotoxic. These T cells share phenotypic and functional properties of natural killer cells, strongly expressing CD57 but lacking the lymphocyte marker CD7. MHC class I recognizing and activating natural killer cell receptors on the surface of CD4+CD28- T cells may be involved in a HLA-B27 mediated co-stimulation of these proinflammatory and cytotoxic cells. 相似文献
16.
17.
Cao D van Vollenhoven R Klareskog L Trollmo C Malmström V 《Arthritis research & therapy》2004,6(4):R335-R346
CD25+CD4+ regulatory T cells participate in the regulation of immune responses. We recently demonstrated the presence of CD25brightCD4+ regulatory T cells with a capacity to control T cell proliferation in the joints of patients with rheumatoid arthritis. Here,
we investigate a possible accumulation of these regulatory T cells in the inflamed joint of different rheumatic diseases including
rheumatoid arthritis. The studies are also extended to analyze whether cytokine production can be suppressed by the regulatory
T cells. Synovial fluid and peripheral blood samples were obtained during relapse from 36 patients with spondyloarthropathies,
21 adults with juvenile idiopathic arthritis and 135 patients with rheumatoid arthritis, and the frequency of CD25brightCD4+ T cells was determined. Of 192 patients, 182 demonstrated a higher frequency of CD25brightCD4+ T cells in synovial fluid than in peripheral blood. In comparison with healthy subjects, the patients had significantly fewer
CD25brightCD4+ T cells in peripheral blood. For functional studies, synovial fluid cells from eight patients were sorted by flow cytometry,
and the suppressive capacity of the CD25brightCD4+ T cells was determined in in vitro cocultures. The CD25brightCD4+ T cells suppressed the production of both type 1 and 2 cytokines including interleukin-17, as well as proliferation, independently
of diagnosis. Thus, irrespective of the inflammatory joint disease investigated, CD25brightCD4+ T cells were reduced in peripheral blood and enriched in the joint, suggesting an active recruitment of regulatory T cells
to the affected joint. Their capacity to suppress both proliferation and cytokine secretion might contribute to a dampening
of local inflammatory processes. 相似文献
18.
Pawlik A Ostanek L Brzosko I Brzosko M Masiuk M Machalinski B Gawronska-Szklarz B 《Arthritis research & therapy》2003,5(4):R210-R213
Clonal expansion of CD4+CD28- T cells is a characteristic finding in patients with rheumatoid arthritis (RA). Expanded CD4+ clonotypes are present in the peripheral blood, infiltrate into the joints, and persist for years. CD4+CD28- T cells are oligoclonal lymphocytes that are rare in healthy individuals but are found in high percentages in patients with
chronic inflammatory diseases. The size of the peripheral blood CD4+CD28- T-cell compartment was determined in 42 patients with RA and 24 healthy subjects by two-color FACS analysis. The frequency
of CD4+CD28- T cells was significantly higher in RA patients than in healthy subjects. Additionally, the number of these cells was significantly
higher in patients with extra-articular manifestations and advanced joint destruction than in patients with limited joint
manifestations. The results suggest that the frequency of CD4+CD28- T cells may be a marker correlating with extra-articular manifestations and joint involvement. 相似文献
19.
Listeria monocytogenes-based vaccines for HER-2/neu are capable of breaking tolerance in FVB/N rat HER-2/neu transgenic mice. The growth of implanted
NT-2 tumors, derived from a spontaneously occurring tumor in the FVB/N HER-2/neu transgenic mouse, was significantly slower
in these mice following vaccination with a series of L. monocytogenes-based vaccines for HER-2/neu. Mechanisms of T cell tolerance that exist in these transgenic mice include the absence of functional
high avidity anti-HER-2/neu CD8+ T cells and the presence of CD4+CD25+ regulatory T cells. The in vivo depletion of these regulatory T cells resulted in the slowing in growth of tumors even without
the treatment of mice with an anti-HER-2/neu vaccine. The average avidities of responsive CD8+ T cells to six of the nine epitopes in HER-2/neu we examined, four of which were identified in this study, are shown here
to be of a lower average avidity in the transgenic mice versus wild type FVB/N mice. In contrast, the average avidity of CD8+ T cells to three epitopes that showed the lowest avidity in the wild-type mice did not differ between wild type and transgenic
mice. This study demonstrates the ability of L. monocytogenes-based vaccines to impact upon tolerance to HER-2/neu in FVB/N HER-2/neu transgenic mice and further defines some of the aspects of tolerance in these mice. 相似文献
20.
Targeting interleukin-2 (IL-2) and/or agonist anti-CD40 antibody (Ab) into tumors represents an effective vaccination strategy
that avoids systemic toxicity and resolves treated-site tumors. Here, we examined IL-2 and/or anti-CD40 Ab-driven local versus
systemic T cell function and the installation of T cell memory. Single tumor studies showed that IL-2 induced a potent CD4+ and CD8+ T cell response that was limited to the draining lymph node and treated-site tumor, and lymph node tumor-specific CD8+ T cells did not upregulate CD44. A two-tumor model showed that while IL-2-treated-site tumors resolved, distal tumors continued
to grow, implying limited systemic immunity. In contrast, anti-CD40 Ab treatment with or without IL-2 expanded the systemic
T cell response to non-draining lymph nodes, and distal tumors resolved. Tumor-specific T cells in lymph nodes of anti-CD40
Ab ± IL-2-treated mice upregulated CD44, demonstrating activation and transition to effector/memory migratory cells. While
CD40-activated CD4+ T cells were not required for eradicating treated-site tumors, they, plus CD8+ T cells, were crucial for removing distal tumors. Rechallenge/depletion experiments showed that the effector/memory phase
required the presence of previously CD40/IL-2-activated CD4+ and CD8+ T cells to prevent recurrence. These novel findings show that different T cell effector mechanisms can operate for the eradication
of local treated-site tumors versus untreated distal tumors and that signaling through CD40 generates a whole of body, effector/memory
CD4+ and CD8+ T cell response that is amplified and prolonged via IL-2. Thus, successful immunotherapy needs to generate collaborating
CD4+ and CD8+ T cells for a complete long-term protective cure. 相似文献