Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CTL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed2005

Rapid functional exhaustion and deletion of CTL following immunization with recombinant adenovirus.

Replication-deficient adenoviruses (recombinant adenovirus (rec-AdV)) expressing different transgenes are widely used vectors for gene therapy and vaccination. In this study, we describe the tolerization of transgene-specific CTL following administration of beta-galactosidase (beta gal)-recombinant adenovirus (Ad-LacZ). Using MHC class I tetramers to track beta gal-specific CTL, we found that a significant expansion of beta gal-specific CTL was restricted to a very narrow dose range. Functional analysis revealed that adenovirus-induced beta gal-specific CTL produced only very low amounts of effector cytokines and were unable to exhibit cytolytic activity in a 51Cr release assay. Furthermore, Ad-LacZ vaccination failed to efficiently clear established beta gal-positive tumors. The impaired function of Ad-LacZ-induced CTL correlated with the presence of persisting beta gal Ag in the liver. A further increase in the peripheral Ag load by injection of Ad-LacZ into SM-LacZ transgenic mice which express beta gal as self-Ag exclusively in peripheral nonlymphoid organs, resulted in the physical deletion of beta gal-specific CTL. Our results indicate first that CTL deletion in the course of adenoviral vaccination is preceded by their functional impairment and second, that the outcome of rec-AdV vaccination depends critically on the Ag load in peripheral tissues.

Adenoviridae↗
PubMed2005

Alpha E beta 7 (CD103) expression identifies a highly active, tonsil-resident effector-memory CTL population.

The characterization of antiviral CTL responses has largely been limited to assessing Ag-specific immune responses in the peripheral blood. Consequently, there is an incomplete understanding of the cellular immune responses at mucosal sites where many viruses enter and initially replicate and how the Ag specificity and activation status of CTL derived from these mucosal sites may differ from that of blood-derived CTL. In this study, we show that EBV-specific CTL responses in the tonsils are of comparable specificity and breadth but of a significantly higher magnitude compared with responses in the peripheral blood. EBV-specific, tonsil-resident, but not PBMC-derived, T cells expressed the integrin/activation marker CD103 (alphaEbeta7), consistent with the detection of its ligand, E-cadherin, on tonsillar squamous cells. These CD8-positive, CD103-positive, tonsil-derived CTL were largely CCR7- and CD45RA- negative effector-memory cells and responded to lower Ag concentrations in in vitro assays than their CD103-negative PBMC-derived counterparts. Thus, EBV-specific CTL in the tonsil, a crucial site for EBV entry and replication, are of greater magnitude and phenotypically distinct from CTL in the peripheral blood and may be important for effective control of this orally transmitted virus.

Antigens, Viral↗
PubMed2006

CD4+ T cells can protect APC from CTL-mediated elimination.

Professional APC play a central role in generating antiviral CD8(+) CTL immunity. However, the fate of such APC following interaction with these same CTL remains poorly understood. We have shown previously that prolonged Ag presentation persists in the presence of a strong CTL response following HSV infection. In this study, we examined the mechanism of survival of APC in vivo when presenting an immunodominant determinant from HSV. We show that transferred peptide-labeled dendritic cells were eliminated from draining lymph nodes in the presence of HSV-specific CTL. Maturation of dendritic cells with LPS or anti-CD40 before injection protected against CTL lysis in vivo. Furthermore, endogenous APC could be eliminated from draining lymph nodes early after HSV infection by adoptive transfer of HSV-specific CTL, yet the cotransfer of significant virus-specific CD4(+) T cell help promoted prolonged Ag presentation. This suggests that Th cells may assist in prolonging class I-restricted Ag presentation, potentially enhancing CTL recruitment and allowing more efficient T cell priming.

Adoptive Transfer↗
PubMed2006

CTL adoptive immunotherapy concurrently mediates tumor regression and tumor escape.

Tumor escape and recurrence are major impediments for successful immunotherapy. It is well-documented that the emergence of Ag-loss variants, as well as regulatory mechanisms suppressing T cell function, have been linked to inadequate antitumor activity. However, little is known regarding the role of Fas-mediated cytotoxicity by tumor-specific CD8(+) CTL in causing immune evasion of Fas resistant variants during adoptive immunotherapy. In this study, we made use of an adoptive transfer model of experimental lung metastasis using tumor-specific CTL as a relevant immune-based selective pressure, and wherein the Fas ligand pathway was involved in the antitumor response. Surviving tumor cells were recovered and examined for alterations in antigenic, functional, and biologic properties. We showed that diminished susceptibility to Fas-mediated cytotoxicity in vivo was an important determinant of tumor escape following CTL-based immunotherapy. Tumor escape variants (TEV) recovered from the lungs of CTL-treated mice exhibited more aggressive behavior in vivo. However, these TEV retained relevant MHC class I and tumor Ag expression and sensitivity to CTL via the perforin pathway but reduced susceptibility to Fas-mediated lysis. Moreover, TEV were significantly less responsive to eradication by CTL adoptive immunotherapy paradigms as a consequence of increased Fas resistance. Overall, we identified that Fas(low)-TEV emerged as a direct consequence of CTL-tumor interactions in vivo, and that such an altered neoplastic Fas phenotype compromised immunotherapy efficacy. Together, these findings may have important implications for both tumor progression and the design of immunotherapeutic interventions to confront these selective pressures or escape mechanisms.

Animals↗
PubMed1999

Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes.

We engineered a multiepitope DNA minigene encoding nine dominant HLA-A2.1- and A11-restricted epitopes from the polymerase, envelope, and core proteins of hepatitis B virus and HIV, together with the PADRE (pan-DR epitope) universal Th cell epitope and an endoplasmic reticulum-translocating signal sequence. Immunization of HLA transgenic mice with this construct resulted in: 1) simultaneous CTL induction against all nine CTL epitopes despite their varying MHC binding affinities; 2) CTL responses that were equivalent in magnitude to those induced against a lipopeptide known be immunogenic in humans; 3) induction of memory CTLs up to 4 mo after a single DNA injection; 4) higher epitope-specific CTL responses than immunization with DNA encoding whole protein; and 5) a correlation between the immunogenicity of DNA-encoded epitopes in vivo and the in vitro responses of specific CTL lines against minigene DNA-transfected target cells. Examination of potential variables in minigene construct design revealed that removal of the PADRE Th cell epitope or the signal sequence, and changing the position of selected epitopes, affected the magnitude and frequency of CTL responses. Our results demonstrate the simultaneous induction of broad CTL responses in vivo against multiple dominant HLA-restricted epitopes using a minigene DNA vaccine and underline the utility of HLA transgenic mice in development and optimization of vaccine constructs for human use.

Amino Acid Sequence↗
PubMed1999

Cross-recognition of two middle T protein epitopes by immunodominant polyoma virus-specific CTL.

We recently identified the immunodominant epitope for polyoma virus-specific CTL as the Dk-associated peptide MT389-397 derived from the middle T (MT) viral oncoprotein. Another Dk-restricted peptide corresponding to residues 236-244 of MT was recognized by nearly all MT389-397-reactive CTL clones, but required concentrations at least 2 logs higher to sensitize syngeneic target cells for lysis. Except for identity at the three putative Dk-peptide anchor residues, MT236-244 shares no homology with MT389-397. Using a novel europium-based class I MHC-peptide binding immunoassay, we determined that MT236-244 bound Dk 2-3 logs less well than MT389-397. Infection with a mutant polyoma virus whose MT is truncated just before the MT389-397 epitope or immunization with MT389-397 or MT236-244 peptides elicited CTL that recognized both MT389-397 and MT236-244. Importantly, infection with a polyoma virus lacking MT389-397 and mutated in an MT236-244 Dk anchor position induced polyoma virus-specific CTL recognizing neither MT389-397 nor MT236-244 epitopes. Despite predominant usage of the Vbeta6 gene segment, MT389-397/MT236-244 cross-reactive CTL clones possess diverse complementarity-determining region 3beta domains; this is functionally reflected in their heterogeneous recognition patterns of alanine-monosubstituted MT389-397 peptides. Using Dk/MT389-397 tetramers, we directly visualized MT236-244 peptide-induced TCR down-modulation of virtually all MT389-397-specific CD8+ T cells freshly explanted from polyoma-infected mice, suggesting that a single TCR recognizes both Dk-restricted epitopes. The availability of immunodominant epitope-specific CTL capable of recognizing a second epitope in MT, a viral protein essential for tumorigenesis, may serve to amplify the CTL response to the immunodominant epitope and prevent the emergence of immunodominant epitope-loss viruses and virus-induced tumors.

Animals↗
PubMed1999

Emergence of CTL coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys.

The CTL response was characterized during primary SIV/macaque (SIVmac) infection of rhesus monkeys to assess its role in containing early viral replication using both an epitope-specific functional and an MHC class I/peptide tetramer-binding assay. The rapid expansion of a single dominant viral epitope-specific CTL population to 1.3-8.3% of circulating CD8+ peripheral blood and 0. 3-1.3% of lymph node CD8+ T cells was observed, peaking at day 13 following infection. A subsequent decrease in number of these cells was then demonstrated. Interestingly, the percent of tetramer-binding CD8+ T cells detected in the lymph nodes of all evaluated animals was smaller than the percent detected in PBL. These epitope-specific CD8+ T cells expressed cell surface molecules associated with memory and activation. Early clearance of SIVmac occurred coincident with the emergence of the CTL response, suggesting that CTL may be important in containing virus replication. A higher percent of annexin V-binding cells was detected in the tetramer+ CD8+ T cells (range, from 33% to 75%) than in the remaining CD8+ T cells (range, from 3.3% to 15%) at the time of maximum CTL expansion in all evaluated animals. This finding indicates that the decrease of CTL occurred as a result of the death of these cells rather than their anatomic redistribution. These studies provide strong evidence for the importance of CTL in containing AIDS virus replication.

Animals↗
PubMed1999

Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL.

We have shown previously that cultured HUVEC or mixtures of endothelial cells (EC) and B lymphoblastoid cells (BLC) induce the differentiation of purified CD8+ PBL into allospecific, class I MHC-restricted CTL that lyse EC, but not BLC autologous to EC. Furthermore, these EC-selective CTL lines secrete little IFN-gamma after target cell contact. In the present study, we have analyzed these polyclonal populations at a single cell level by cloning at limiting dilution and propagating the resulting CTL clones in the absence of EC. Phenotypically stable, alloreactive EC-selective CTL preferentially emerge from cocultures in which EC or EC + BLC are the initial stimulating cell types compared with cocultures stimulated by BLC alone (p = 0.005). Compared with BLC-stimulated CTL, EC-stimulated CTL clones often fail to secrete IFN-gamma after target cell contact (p = 0.0006) and constitutively express CD40 ligand (CD40L) at rest (p = 0.0006). The absence of IFN-gamma secretion does not result from a switch to IL-4 secretion. The expression of CD40L inversely correlates with the secretion of IFN-gamma after target cell contact (p = 0.0001), but correlations of CD40L expression and failure to secrete IFN-gamma with EC-selective killing did not reach statistical significance. We conclude that in a microenvironment in which allogeneic EC are in close contact with infiltrating CD8+ T cells, such as within a graft arterial intima, CTL subsets may emerge that display EC selectivity or express CD40L and secrete little IFN-gamma after Ag contact.

Cell Differentiation↗
PubMed1999

Human virus-specific CD8+ CTL clones revert from CD45ROhigh to CD45RAhigh in vivo: CD45RAhighCD8+ T cells comprise both naive and memory cells.

It has been generally believed that human CD8+ memory cells are principally found within the CD45ROhigh population. There are high frequencies of CD8+ memory CTL specific for the human CMV tegument phosphoprotein pp65 in PBMC of long-term virus carriers; the large population of memory CTL specific for a given pp65 peptide contains individual CTL clones that have greatly expanded. In this study, we found high frequencies of pp65 peptide-specific memory CTL precursors in the CD45ROhighCD45RA- population, but also appreciable frequencies in the CD45RAhigh subpopulation. Because the majority of CD8+ T cells in PBMC are CD45RAhigh, more of the total pp65-specific memory CTL pool is within the CD45RAhigh than in the CD45ROhigh compartment. Using clonotypic oligonucleotide probes to quantify the size of individual pp65-specific CTL clones in vivo, we found the CD45RAhigh population contributed 6- to 10-fold more than the CD45ROhigh population to the total virus-specific clone size in CD8+ cells. During primary CMV infection, an individual virus-specific CTL clone was initially CD45ROhigh, but after resolution of infection this clone was detected in both the CD45ROhigh and the CD45RAhigh populations. We conclude that CD45RA+ human CD8+ T cells do not solely comprise naive cells, but contain a very significant proportion of memory cells, which can revert from the CD45ROhigh to CD45RAhigh phenotype in vivo.

Carrier State↗
PubMed1999

Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas.

Twenty-two new HLA-A2.1-binding peptides derived from the protooncogene HER2/neu were identified and analyzed for their capacity to elicit peptide and tumor-specific CTL responses. We used peptide-pulsed autologous DC from the ascites of patients with ovarian carcinomas to induce CTL. Of the 22 tested new HER2/neu-derived epitopes that could bind HLA-A2 with high (IC50 < 50 nM) or intermediate (50 nM < IC50 < 500 nM) affinity, we report the recognition by CTL of at least four novel epitopes, including HER2(9435), HER2(9665), HER2(9689), and HER2(10952), and confirm that of the known HER2 (9369) epitope. These epitopes were able to elicit CTL that specifically killed peptide-sensitized target cells and, most importantly, a HER2/neu-transfected cell line and the autologous tumor cells. We also confirm that HER2/neu is overexpressed in several melanoma lines, and as a new finding, report that some of these lines are sensitive to CTL induced by the HER2 (9369), HER2(9435), and HER2(9689) epitopes. Finally, CTL clones specific for HER2 (9369), HER2(9435), and HER2(9689) epitopes were isolated from tumor-specific CTL lines, further demonstrating the immunodominance of these epitopes. These findings broaden the potential application of HER2/neu-based immunotherapy.

Carcinoma↗
PubMedDate not supplied

Folate binding protein peptide 191-199 presented on dendritic cells can stimulate CTL from ovarian and breast cancer patients.

Tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumor responses are mediated by cytotoxic T lymphocytes (CTL) which recognize antigen in the context of MHC molecules using T cell receptors. CD8+ CTL recognize peptide epitopes processed from cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% of breast cancers. We recently found that FBP is the source of antigenic peptides recognized by a number of these CTL-TAL. This indicated that FBP peptides are antigenic in vivo for ovarian and breast CTL-TAL. To define FBP immunogenicity, a peptide defining the epitope E39 (FBP, 191-199) was presented by PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulation of ovarian and breast CTL-TAL by E39 pulsed DC (DC-E39), in the presence of IL-2, rapidly enhanced or induced E39 specific CTL activity. This E39-responder population consisted of cells expressing TCR V beta 9, V beta 13, and V beta 17 families, based on the increase in the percentages of these families in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogenic tumor antigens and of cytokine requirements for induction of functional antitumor effectors may be important for future cancer vaccine developments.

Breast Neoplasms↗
PubMed2001

Endogenous expression and HLA stabilization assay of Plasmodium falciparum CTL epitope minigene in human HLA-A2. 1 and HLA-B51 cells.

OBJECTIVE: To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. METHODS: Synthesized oligonucleotides encoding for P. f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT-PCR and HLA stabilization assay. RESULTS: Two mini-genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA-B51, SH6 which was restricted to HLA-A2. 1, and TS, which had the two aforementioned mini-genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini-gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. CONCLUSION: A successful expression and presentation of multiple CTL epitope mini-gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope Plasmodium falciparum DNA vaccine that could cover most of Chinese population.

Animals↗
PubMed2004

Combined transfection with EBV-specific epitopes and HLA-A2 genes is more effective than separate transfection in promoting CTL lysis against nasopharyngeal carcinoma.

To augment specific cytotoxic T lymphocyte (CTL) lysis is a promising strategy for cancer therapy. In this study, we examined the boosting effect of CTLs upon autologous lymphoblastoid B cell lines (LCLs) transfected with diverse plasmids, to explore the possible CTL-based immunotherapy of nasopharyngeal carcinoma (NPC). FCM analysis displayed rather high ratio (>30%) of successfully transfected LCLs by utilizing the DMRIE-C kit. CTL assays demonstrated that substantially higher ratio of CTL specific lysis was observed upon the LCLs transfected with both expression vectors encoding EBV-specific epitopes and their presentation molecule HLA-A2, in contrast with those transfected separately. By transfecting the vector encoding HLA-A2 alone, only the LCLs of HLA-A2(+) donors elicited markedly higher CTL lysis. CTL assays also showed that there existed no marked differences upon transfection by either different vectors (pcDNA3, pNGVL3 or pNGVL3-hFlex), or different EBV-derived peptides (LMP(2)Pep1 or LMP(2)Pep2), or with or without the doubled DNA sequence encoding peptides. This study indicated a promising immunotherapy strategy on NPC through boosting and eliciting the EBV-specific CTL activation by transferring vectors encoding both EBV-specific epitopes and their presentation molecule HLA-A2 into autologous LCL, the presentation cells of MHC/peptide tetrameric complex.

Adult↗
PubMed2006

[Quantification and phenotypic analysis of hCMV specific CTL in peripheral blood from HLA-A2+ donors].

AIM: To optimize tetramer staining condition using HLA-A*0201 tetramer (A2-NLV tetramer) loaded with NLV peptide (pp65(495-503)) derived from structural protein pp65 of human cytomegalovirus and to investigate its application in phenotyping of specific cytotoxic T lymphocytes (CTL). METHODS: Peripheral blood from HLA-A2(+) donors was first stained with A2-NLV tetramer/PE under different conditions and then labeled with anti-CD3-FITC and anti-CD8-APC. The stained samples were analyzed with flow cytometry to find out the optimized staining condition. Meanwhile, the phenotype and activation antigen expression were determined. RESULTS: Tetramer staining with whole blood was superior to peripheral blood mononuclear cells. The optimized condition for tetramer staining was incubating 100 muL of whole blood with 0.3 mug of A2-NLV tetramer for 1 h at 4 degrees Celsius. Under this condition the specific staining was strong while unspecific staining of CD8(-) T cells was quite weak. Phenotypic analysis under this condition showed that the ratio of CD28 positive A2-NLV tetramer specific CTL was lower than that of nonspecific CTL, whereas the ratio of CD57 positive specific CTL was higher than that of nonspecific CTL. CD25 molecules were only expressed on the activated specific CTL. CONCLUSION: The optimized tetramer staining condition can increase the specificity of tetramer staining and decrease unspecific binding, therefore it is applicable for phenotyping and functional analysis of antigen-specific CTL.

Adult↗
PubMed1986

Cytotoxic lymphokines produced by cloned human cytotoxic T lymphocytes. II. A novel CTL-produced cytotoxin that is antigenically distinct from tumor necrosis factor and alpha-lymphotoxin.

We have cloned lines of IL 2-dependent human T cells derived from alloantigen, soluble antigen (tetanus toxoid), mitogen, or IL 2-stimulated peripheral blood lymphocytes and characterized their surface marker expression and cytolytic activity. The surface phenotype and cytolytic function was compared with the ability of these T cell clones to release cytotoxic lymphokines in response to mitogenic lectins. The cytotoxins released by these CTL clones were detected on the murine L929 target cells in a 16-hr assay. All of the T cell clones, whether stimulated by HLA alloantigens, tetanus toxoid, or mitogens, exhibited killer cell activity and the capacity to secrete a soluble cytotoxin(s). Specific polyclonal antisera to recombinant human tumor necrosis factor (rTNF) and human alpha-lymphotoxin (alpha LT) were unable to neutralize the cytotoxic activity released by most of these CTL clones. These results indicate that human CTL produce a novel antigenic form(s) of cytotoxin that we have termed CTL-toxin. Supernatants from several CTL clones yielded a cytotoxic activity that was partially neutralized (10 to 40%) by saturating levels of anti-TNF (but not anti-alpha LT) indicating that human CTL may be capable of producing a TNF-like molecule. Only two out of 60 CTL clones studied thus far produced a cytotoxic activity that was partially neutralized by anti-alpha LT (20 to 40%). Collectively, these results suggest that although both the CD4 and the CD8 subpopulations of human cytotoxic T cells may be capable of releasing several types of cytotoxins in response to mitogenic signals, the predominant cytotoxin is distinct from alpha LT and TNF.

Antibodies, Monoclonal↗
PubMed1986

Generation of cytotoxic T lymphocytes from thymocyte precursors to trinitrophenyl-modified self antigens. I. Requirement of both killer-helper factor(s) and interleukin 2 for CTL generation from a subpopulation of thymocytes.

The requirement for signals in the induction of cytotoxic T lymphocytes (CTL) from thymocyte precursors has been investigated. Either unfractionated or peanut agglutinin-binding (PNA+) C3H/He thymocytes were stimulated with mitomycin C(MMC)-treated, 2,4,6-trinitrophenyl(TNP)-modified syngeneic spleen cells in the presence of a variety of lymphokine preparations. Cellfree supernatant (CFS) from purified protein derivatives(PPD-CFS) stimulated Mycobacterium tuberculosis (Tbc)-primed cells, or partially purified interleukin 2 (IL 2) mediated strong cytotoxic responses in unfractionated thymocytes, whereas only PPD-CFS at final concentrations beyond 30% was active for CTL generation in PNA+ thymocytes. Neither IL 2 at concentrations of below 60 U/ml nor a low concentration of PPD-CFS (at final below 10%) had such a capacity. The addition of monoclonal anti-IL 2 receptor antibody completely blocked CTL generation induced by PPD-CFS in PNA+ thymocytes. In contrast, anti-immune interferon (IFN-gamma) antibody showed a marginal effect. PPD-CFS (10%) and IL 2 (10 U/ml) could synergistically trigger PNA+ thymocytes to induce CTL generation. These results suggested that both IL 2 and "helper" factors other than IL 2 are required for CTL generation from PNA+ thymocytes. We refer to these kinds of helper factors as killer helper factors (KHF). Partially purified IL 2-free KHF show two peaks of activities at apparent m.w. 14,000 to 34,000 and 44,000 to 90,000, and are heterogeneous with respect to isoelectric point, which is between 4.5 and 5.1. Cultures that received TNP-modified syngeneic cells and KHF on day 0 and IL 2 on day 2 generated potent CTL responses, whereas the addition of IL 2 on day 0 followed by the addition of KHF on day 2 to the culture was ineffective, suggesting that KHF is required in the early phase of the culture to achieve optimal CTL responses.

Animals↗
PubMed1987

Frequency analysis of augmented CTL production associated with Corynebacterium parvum-induced tumour regression.

A limiting-dilution frequency assay was employed to estimate the increased production of cytolytic T lymphocytes (CTL) associated with Corynebacterium parvum-induced regression of the P815 mastocytoma growing subcutaneously in semisyngeneic mice. It was found that intratumour C. parvum functioned to augment greatly the underlying concomitant production of CTL that occurs normally in response to a progressively growing untreated immunogenic tumour. The lymph node draining a C. parvum-treated tumour contained about eight times more CTL than the lymph node draining a control tumour. Intratumour C. parvum also caused a large increase in CTL production in the spleen and an increase in the number of CTL that could accumulate in a peritoneal exudate. At the peak of the anti-tumour response, the largest number of CTL was found in the draining lymph node (1.66 X 10(5], followed by the spleen (3.47 X 10(4) and by a 24-hr casein-induced peritoneal exudate (6.01 X 10(3]. Presumably, this greatly augmented production of CTL explains why C. parvum given intralesionally early enough during tumour growth can cause the regression of the weakly immunogenic P815 mastocytoma.

Animals↗
PubMed1986

Gene mapping and somatic cell hybrid analysis of the role of human lymphocyte function-associated antigen-3 (LFA-3) in CTL-target cell interactions.

LFA-3 is expressed on a wide variety of human cell lines, including those which have been used as recipients for gene transfer of human class I gene products, whereas a murine counterpart is either absent or significantly different such that the anti-LFA-3 monoclonal antibody (MAb) does not bind. By using a somatic cell genetic approach, we demonstrate that LFA-3 is not a major histocompatibility complex-encoded molecule, and that its gene locus maps to human chromosome 1. When LFA-3 and HLA-A2 are coexpressed on the mouse cell surface, anti-LFA-3 MAb interfered with specific recognition and lysis of these target cells by human CTL capable of lysing HLA-A2-expressing mouse transfectants. A significant contribution of the LFA-3 molecule to CTL reactivity was not observed, however, because the presence of LFA-3 did not restore recognition by CTL clones previously found incapable of lysing HLA-A2-expressing mouse transfectants, nor was it required by those human CTL that could lyse mouse cell transfectants. Thus, we have used genetic techniques to demonstrate that LFA-3 may serve a role in CTL-target cell interactions at the target cell level, but is not a molecule absolutely required for human allospecific CTL recognition of HLA antigens expressed on mouse cells. We suggest that LFA-3 may not participate directly in CTL function under normal circumstances, but delivers a more general inhibitory signal only when provoked by bound MAb.

Animals↗