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PubMed1987

Effector cells in allelic H-2 class I-incompatible skin graft rejection.

The cellular mechanisms of skin graft rejection with allelic H-2 class I differences were studied by examining the effect on graft survival of in vivo administration of anti-Lyt-2.2 mAb, anti-L3T4 mAb, or both to recipient mice. The injections of anti-Lyt-2.2 mAb and anti-L3T4 mAb caused selective depletions of Lyt-2+ cells and L3T4+ cells, respectively. Injection of anti-Lyt-2.2 mAb significantly prolonged graft survival in 7 of 12 combinations of H-2D-end difference, but did not prolong graft survival in 5 other combinations of H-2D-end difference, or in 2 combinations of H-2K-end difference. Injection of anti-L3T4 mAb did not prolong graft survival in any combinations with class I difference tested. Injection of anti-L3T4 mAb plus anti-Lyt-2.2 mAb markedly prolonged graft survival in the combinations with class I difference in which anti-Lyt-2.2 mAb had no effect and overcame the effect of anti-Lyt-2.2 mAb in those in which anti-Lyt-2.2 mAb had an effect in prolonging graft survival. These results indicated that in combinations in which anti-Lyt-2.2 mAb did not prolong graft survival, class I antigen stimulated L3T4+ effector cells when Lyt-2+ cells were blocked and Lyt-2+ effector cells when L3T4+ cells were blocked. On the other hand, in the combinations in which anti-Lyt-2.2 mAb prolong graft survival, these antigens initially caused preferential stimulation of Lyt-2+ but not L3T4+ effector cells, although delayed activation of L3T4+ effector cells occurred when Lyt-2+ cells were blocked. Furthermore, a significant correlation was found between the effect of anti-Lyt-2.2 mAb in prolonging graft survival and the failure of recipient mice to produce H-2 antibody. These results can be taken as evidence that L3T4+ effector cells are not involved in the initial phase of graft rejection in these combinations.

Alleles↗
PubMed2004

Ypt31/32 GTPases and their novel F-box effector protein Rcy1 regulate protein recycling.

Ypt/Rab GTPases control various aspects of vesicle formation and targeting via their diverse effectors. We report a new role for these GTPases in protein recycling through a novel effector. The F-box protein Rcy1, which mediates plasma membrane recycling, is identified here as a downstream effector of the Ypt31/32 GTPase pair because it binds active GTP-bound Ypt31/32 and colocalizes with these GTPases on late Golgi and endosomes. Furthermore, Ypt31/32 regulates the polarized localization and half-life of Rcy1. This suggests that Ypt/Rabs can regulate the protein level of their effectors, in addition to the established ways by which they control their effectors. We show that like Rcy1, Ypt31/32 regulate the coupled phosphorylation and recycling of the plasma membrane v-SNARE Snc1. Moreover, Ypt31/32 and Rcy1 regulate the recycling of the furin-homolog Kex2 to the Golgi. Therefore, Ypt31/32 and Rcy1 mediate endosome-to-Golgi transport, because this is the only step shared by Snc1 and Kex2. Finally, we show that Rcy1 physically interacts with Snc1. Based on this result and because F-box proteins serve as adaptors between specific substrates and ubiquitin ligases, we propose that Ypt31/32 GTPases regulate the function of Rcy1 in the phosphorylation and/or ubiquitination of proteins that recycle through the Golgi.

Blotting, Western↗
PubMed2003

IL-15 enhances the function and inhibits CD95/Fas-induced apoptosis of human CD4+ and CD8+ effector-memory T cells.

Although the effect of IL-15 has been described on murine cells in vitro and in vivo, its effect on human memory CD8(+) T cells is not well characterized. We show here that IL-15 preferentially enhances the activation and effector function of human effector-memory CD45RA(-)CD62L(-) and CD45RA(+)CD62L(-) CD4(+) and CD8(+) T cells in both healthy and HIV-infected individuals. We find that IL-15 increases 2- to 5-fold both the activation and secretion of the effector cytokines IFN-gamma and tumor necrosis factor (TNF)-alpha by anti-CD3-stimulated purified CD4(+) and CD8(+) T cells and peripheral blood mononuclear cells from healthy and HIV-infected individuals. Furthermore, IL-15 potently inhibits CD95/Fas-induced apoptosis of the effector-memory CD4(+) and CD8(+) T cells from HIV-infected individuals. These findings suggest that in addition to being a growth and survival factor for memory CD8(+) T cells, IL-15 is also a potent activator of human effector-memory CD8(+) T cells both in healthy and in HIV-infected individuals.

Adolescent↗
PubMed2006

Bioinformatics-enabled identification of the HrpL regulon and type III secretion system effector proteins of Pseudomonas syringae pv. phaseolicola 1448A.

The ability of Pseudomonas syringae pv. phaseolicola to cause halo blight of bean is dependent on its ability to translocate effector proteins into host cells via the hypersensitive response and pathogenicity (Hrp) type III secretion system (T3SS). To identify genes encoding type III effectors and other potential virulence factors that are regulated by the HrpL alternative sigma factor, we used a hidden Markov model, weight matrix model, and type III targeting-associated patterns to search the genome of P. syringae pv. phaseolicola 1448A, which recently was sequenced to completion. We identified 44 high-probability putative Hrp promoters upstream of genes encoding the core T3SS machinery, 27 candidate effectors and related T3SS substrates, and 10 factors unrelated to the Hrp system. The expression of 13 of these candidate HrpL regulon genes was analyzed by real-time polymerase chain reaction, and all were found to be upregulated by HrpL. Six of the candidate type III effectors were assayed for T3SS-dependent translocation into plant cells using the Bordetella pertussis calmodulin-dependent adenylate cyclase (Cya) translocation reporter, and all were translocated. PSPPH1855 (ApbE-family protein) and PSPPH3759 (alcohol dehydrogenase) have no apparent T3SS-related function; however, they do have homologs in the model strain P. syringae pv. tomato DC3000 (PSPTO2105 and PSPTO0834, respectively) that are similarly upregulated by HrpL. Mutations were constructed in the DC3000 homologs and found to reduce bacterial growth in host Arabidopsis leaves. These results establish the utility of the bioinformatic or candidate gene approach to identifying effectors and other genes relevant to pathogenesis in P. syringae genomes.

Adenylyl Cyclases↗
PubMed2004

Diverse members of the AvrBs3/PthA family of type III effectors are major virulence determinants in bacterial blight disease of rice.

AvrXa7 is a member of the avBs3/pthA gene family and the only known type III secretion system effector gene from Xanthomonas oryzae pv. oryzae with a major contribution to bacterial growth and lesion formation in bacterial blight disease of rice. We examined the general requirement for effectors of the AvrBs3/PthA family in bacterial blight of rice by identifying effectors from diverse strains of the pathogen. Inactivation of single effector genes in representative strains from Japan, Korea, and the Philippines resulted in severely limited growth in plants. Five strains harbored one gene of the avrBs3/pthA family, while one strain had two genes with the equivalent virulence activity of avrXa7. Sequence analysis revealed three genes with unique repeat arrangements in comparison to avrXa7. Comparison of the repetitive regions revealed a potential motif for the group that was also present in the repetitive region of avrBs3. However, the repetitive region of avrBs3 could not support virulence activity but, in combination with the C-terminal coding region of avrXa7, triggered a Xa7-dependent avirulence reaction. The results revealed diverse members of the avrBs3/pthA gene family with virulence activity in X. oryzae pv. oryzae and supported the hypothesis that bacterial blight disease of rice is highly dependent on a single class of type III effectors. The results also indicated that avrXa7 avirulence specificity is separable from virulence activity.

Bacterial Proteins↗
PubMed1994

Immunization of mice with allogeneic fibroblasts genetically modified for interleukin-2-secretion and expression of melanoma-associated antigens stimulate predetermined classes of anti-melanoma effector cells.

Immunization of C57BL/6 mice (H-2b) with a mouse fibroblast cell-line of C3H origin (H-2k) genetically modified for interleukin-2 (IL-2)-secretion and the expression of melanoma-associated antigens (MAAs) (RLBA-IL-2 cells) resulted in a systemic anti-melanoma cellular immune response that led to a prolongation of survival of mice with established melanoma. Here we report certain of the effector cell-types activated for anti-melanoma immunity in mice immunized with the modified cells and, for comparison, the anti-melanoma cell-types activated following immunization with IL-2-secreting, MAA-negative fibroblasts (LM-IL-2 cells) or with non-IL-2-secreting, MAA-positive fibroblasts (RLBA-ZipNeo cells). The data indicate that both Lyt-2.2+ (CD8+) and natural killer/lymphokine-activated killer (NK/LAK) cells with anti-melanoma cytotoxicity were predominant in mice immunized with RLBA-IL-2 cells. NK/LAK cells alone were predominant in mice immunized with LM-IL-2 cells, and Lyt-2.2+ cells were predominant in mice immunized with RLBA-ZipNeo cells. The involvement of L3T4+ (CD4+) cells in the effector phase of the response was not detected in mice immunized with the genetically modified cells. Immunization of mice with both LM-IL-2 cells and RLBA-ZipNeo cells resulted in an anti-melanoma response of greater magnitude than was present in mice immunized with either cell-construct alone. It was equivalent to the melanoma immunity in mice immunized with RLBA-IL-2 cells. These data indicate that the immunogenic properties of the modified cells determined the anti-melanoma effector cell-types and suggest that combination immunotherapy with cell-constructs that stimulate different classes of effector cells may be more effective in immune-mediated tumor regression than immunization with a construct that activates a single effector cell-type alone.

Animals↗
PubMed1976

The distribution of effector cells for antibody-dependent cytotoxicity is species dependent.

Murine lymphoma cells were lysed by using either an allogeneic or a xenogeneic (rat) antiserum and antibody-dependent effectors from mice and rats. It was found that murine spleens were poorly antibody-dependent effectors against this target. The peritoneal cavities of mice were a good source of effectors. In rats, the spleen contained effectors, whereas adherent cells from the peritoneal cavity were comparatively ineffective. Cells from both rat and murine spleens lysed sheep erythrocytes in conjunction with an appropriate antiserum. The data emphasize that there is a difference in the antibody-dependent lysis of erythrocytes compared to nucleated mammalian cells. They also demonstrate that the distribution of antibody-dependent effectors is species dependent.

Animals↗
PubMed2005

Cytomegalovirus rather than HIV triggers the outgrowth of effector CD8+CD45RA+CD27- T cells in HIV-1-infected children.

OBJECTIVE: To analyse the effect of viral coinfections on immune reconstitution in HIV-1-infected children (< 18 years) taking highly active antiretroviral therapy (HAART). METHODS: Absolute lymphocyte numbers of various subsets of CD8 T cells were measured. RESULTS: Prior cytomegalovirus (CMV) infection correlated with an increased number of CD8 effector T cells (i.e., CD45RA+CD27-) at baseline (CMV-seropositive versus CMV-seronegative patients; P = 0.009), as well as an increased state of T cell activation as defined by HLA-DR and CD38 expression. The expansion of effector CD8 T cells persisted over time, independent of the HIV response to HAART. Numbers of CD8 effector T cells were significantly higher in patients with CMV replication as reflected by persistent urinary CMV shedding and periodic CMV DNAaemia (P = 0.02). These patients also showed an increase in CMV-specific antibodies compared with those without CMV shedding (P = 0.007). The number of CMV-specific interferon-gamma (IFN-gamma)-producing CD8 T cells was lower in children who persistently shed CMV compared with those who did not (P = 0.02). In contrast, CMV-specific CD4 T cell responses were detected at similar levels in both groups. CONCLUSIONS: In HIV-1-infected children, CMV infection correlated with the outgrowth of CD8+CD45RA+CD27- effector T cells. Activation of the immune system by persistent CMV secretion resulted in increasing CMV-specific IgG and higher numbers of CD8 effector T cells. Despite these increases, the CMV-specific IFN-gamma-producing CD8 T cell response was diminished, which could explain the inability to suppress CMV completely in 41% of HIV-1-infected children.

Adolescent↗
PubMed1989

Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes.

Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histocompatibility antigens. This report describes a new approach that employs pretreatment of effector cells with 8-methoxy-psoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Reinfusion of photodamaged cells resulted in an immunosuppressive host response that permitted prolonged retention of histoincompatible skin grafts and specifically inhibited in vitro and in vivo responses that correlate with allograft rejection. Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes served as a source of alloreactive effector cells. The splenocytes were treated with 100 ng/ml 8-MOP and 1 J/cm2 UVA before reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft. Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T cell responses to CBA/j alloantigens in comparison with sensitized and naive controls. Splenocytes from these hyporesponsive mice suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. Moreover, BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 d posttransplantation without visual evidence of rejection. These results indicate that the in vivo and in vitro response to alloantigen can be attenuated by pretreating the host with photoinactivated splenocytes containing the effector cells of alloantigen rejection.

Animals↗
PubMed2006

The fate of effector CD8 T cells in vivo is controlled by the duration of antigen stimulation.

What controls the fate of the T-cell response remains incompletely defined. Gain of effector function facilitated by costimulation has been thought to be a crucial factor in determining the outcome of the T-cell response, i.e. long-term memory in the presence of costimulation versus tolerance induction in the absence of costimulation. In this study, we show that while costimulation or cognate CD4 helps to promote the acquisition of effector function during the initial phase of the CD8 T-cell response, the fate of effector CD8 T cells is controlled by the duration of subsequent antigenic stimulation. Effector CD8 T cells differentiate into memory cells only after clearance of antigen, whereas in the presence of persistent antigen, effector CD8 T cells are tolerized. Furthermore, protective immunity against tumour cannot develop in the persisting antigen environment. These results suggest that removal of persisting antigen by other means might be a prerequisite for effective immunotherapy in cancer.

Adoptive Transfer↗
PubMed2004

SsaM and SpiC interact and regulate secretion of Salmonella pathogenicity island 2 type III secretion system effectors and translocators.

The type III secretion system (TTSS) encoded by Salmonella Pathogenicity Island 2 (SPI-2) is required for systemic infection and intracellular replication of Salmonella enterica serovar Typhimurium. The SPI-2 TTSS is activated after internalization of bacteria by host cells, and translocates effector proteins into and across the vacuolar membrane, where they interfere with several host cell functions. Here, we investigated the function of SsaM, a small protein encoded within SPI-2. An ssaM deletion mutant had virulence and intracellular replication defects comparable to those of a SPI-2 TTSS null mutant. Although the ssaM mutant was able to secrete the effector protein SseJ in vitro, it failed to translocate SseJ into host cells, and to secrete the translocon proteins SseB, SseC and SseD in vitro. This phenotype is similar to that of a strain carrying a mutation in the SPI-2 gene spiC, whose product is reported to be an effector involved in trafficking of the Salmonella vacuole in macrophages. Both ssaM and spiC mutants were found to oversecrete the SPI-2 effector proteins SseJ and PipB in vitro. Fractionation assays and immunofluorescence microscopy were used to investigate the localization of SsaM and SpiC in macrophages. No evidence for translocation of these proteins was obtained. The similar phenotypes of the ssaM and spiC mutants suggested that they might be involved in the same function. Pull-down and co-immune precipitation experiments showed that SpiC and SsaM interact within the bacterial cell. We propose that a complex involving SsaM and SpiC distinguishes between translocators and effector proteins, and controls their ordered secretion through the SPI-2 TTSS.

Animals↗
PubMed2004

The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice.

Salmonella resides within host cells in a vacuole that it modifies through the action of virulence proteins called effectors. Here we examined the role of two related effectors, SopD and SopD2, in Salmonella pathogenesis. Salmonella enterica serovar Typhimurium (S. Typhimurium) mutants lacking either sopD or sopD2 were attenuated for replication in the spleens of infected mice when competed against wild-type bacteria in mixed infection experiments. A double mutant lacking both effector genes did not display an additive attenuation of virulence in these experiments. The double mutant also competed equally with both of the single mutants. Deletion of either effector impaired bacterial replication in mouse macrophages but not human epithelial cells. Deletion of sopD2 impaired Salmonella's ability to form tubular membrane filaments [Salmonella-induced filaments (Sifs)] in infected cells; the number of Sifs decreased, whereas the number of pseudo-Sifs (thought to be a precursor of Sifs) was increased. Transfection of HeLa cells with the effector SifA induced the formation of Sif-like tubules and these were observed in greater size and number after co-transfection of SifA with SopD2. In infected cells, SifA and SopD2 were localized both to Sifs and to pseudo-Sifs. In contrast, deletion of sopD had no effect on Sif formation. Our results indicate that both SopD and SopD2 contribute to virulence in mice and suggest a functional relationship between these two proteins during systemic infection of the host.

Animals↗
PubMed1976

Lymphocyte-mediated cytotoxicity against tumor cells specificity and characterization of concanavalin A-activated cytotoxic effector lymphocytes.

The selective T cell mitogen Con A was found to induce cytotoxic effectorlymphocytes after in vivo or in vitro treatment. The effector cells exhibited immunologic specificity when tested against tumor cells, killing targets only across H-2 histocompatibility barriers. Thus, Con A caused a polyclonal T cell activation, resulting in the appearance of effector cells capable of recognizing all H-2 antigens, except those coded for by the major histocompatibility loci of the lymphocyte donor. These experiments demonstrate that Con A is capable of activating pre-existing T cells to reveal their genetically determined immunological specificity, and furthermore suggest that there is a deletion of T cell clones with specificity for self. The activated effector cells were characterized as T blasts being relatively insensitive to treatment with anti-O serum plus complement. The precursors of the Con A-activated effector cells were shown to reside primarily in the spleen, to be radio-resistant up to 400 R, and to be short-lived after adult thymectomy. Thus, the population of T cells capable of activation to cytotoxic effector lymphocytes by Con A has similar physical characteristics to the splenic subset(s) of T cells mediating both GVH and cytotoxicity responses upon alloimmunization.

Animals↗
PubMed1997

From naive to effector--alterations with aging.

We have used a T-cell receptor transgenic mouse model to study the role of antigen in the changes that occur as T cells age. We find that the characteristic shift in the CD4 population to a predominance of memory phenotype T cells which accompanies aging in non-transgenic mice does not occur, suggesting that this shift is a result of antigenic stimulation. Thus at least one component of aging must be antigen dependent. When responses of naive CD4 T cells from aged and young mice are directly compared in vitro, the former are relatively deficient in their ability to produce IL-2 and IL-3, they express altered levels of P-glycoprotein and they proliferate less well in the absence of exogenous cytokines. When the ability of both naive populations to generate effectors is compared, the number of effectors generated from aged naive cells is much reduced and the effectors generated express lower levels of IL-2R alpha and produce reduced levels of cytokines. Importantly, addition of IL-2 restores proliferation of aged naive T cells, restores efficient effector generation and results in effectors seemingly indistinguishable from those derived from young CD4 cells. Similar phenotypic and functional changes seen with aging are also found in T-cell populations from IL-2 and IL-2R alpha knockout mice. Thus the loss of optimal IL-2 production may participate in the aging process and may represent the main antigen-independent defect in the CD4 T-cell population.

Aging↗
PubMed2006

Functional dissection of SseF, a type III effector protein involved in positioning the salmonella-containing vacuole.

Intracellular replication of Salmonella enterica requires the formation of a unique organelle termed Salmonella-containing vacuole (SCV). The type III secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2-T3SS) has a crucial role in the formation and maintenance of the SCV. The SPI2-T3SS translocates a large number of effector proteins that interfere with host cell functions such as microtubule-dependent transport. We investigated the function of the effector SseF and observed that this protein is required to maintain the SCV in a juxtanuclear position in infected epithelial cells. The formation of juxtanuclear clusters of replicating Salmonella required the recruitment of dynein to the SCV but SseF-deficient strains were highly reduced in dynein recruitment to the SCV. We performed a functional dissection of SseF and defined domains that were important for translocation and the specific effector functions of this protein. Of particular importance was a hydrophobic domain in the C-terminal half that contains three putative transmembrane (TM) helices. Deletion of one of these TM helices ablated the effector functions of SseF. We observed that this domain was essential for the proper intracellular positioning of the SCV to a juxtanuclear, Golgi-associated localization. These data show that SseF, in concert with the effector proteins SifA and SseG mediate the precise positioning of the SCV by differentially modulating the recruitment of microtubule motor proteins to the SCV.

Bacterial Proteins↗
PubMed1998

Secreted effector proteins of Salmonella dublin act in concert to induce enteritis.

The ability of enteropathogenic salmonellae to recruit inflammatory cells and induce secretory responses in the infected ileum is considered to be a main feature in Salmonella-induced enteritis. Interactions between the pathogen and intestinal epithelial cells result in a variety of cellular responses mediating inflammation and fluid secretion. It is becoming apparent that proteins secreted by the Inv-Spa type III secretion system of Salmonella spp. play a key role in the induction of these responses. We have recently demonstrated that the SopB effector protein is translocated into eukaryotic cells via a Sip-dependent pathway and mediates inflammation and fluid secretion in infected ileal mucosa. However, SopB did not appear to be the only effector involved, as inactivation of the sopB gene only partially impaired enteropathogenicity. We suggested that at least some of such protein effectors are likely to be proteins of the same class as SopB, i.e., secreted effector proteins translocated into eukaroyotic cells via a Sip-dependent pathway. In this work, we identify SopD, another secreted protein belonging to the family of Sop effectors of Salmonella dublin. Using the cya reporter system we showed that SopD is translocated into eukaroyotic cells. We assessed the potential involvement of SopD in enteropathogenicity and found that inactivation of sopD has an additive effect in relation to the sopB mutation.

Amino Acid Sequence↗
PubMed2002

SpiC is required for translocation of Salmonella pathogenicity island 2 effectors and secretion of translocon proteins SseB and SseC.

The Salmonella pathogenicity island 2 (SPI2) type III secretion system (TTSS) promotes Salmonella enterica serovar Typhimurium virulence for mice and increased survival and replication within eukaryotic cells. After phagocytosis, Salmonella serovar Typhimurium assembles the SPI2 TTSS to translocate over a dozen effector proteins across the phagosome membrane. SpiC has been previously shown to be a translocated effector with a large contribution to virulence (K. Uchiya, M. A. Barbieri, K. Funato, A. H. Shah, P. D. Stahl, and E. A. Groisman, EMBO J. 18:3924-3933, 1999). This report demonstrates by competitive index that the virulence phenotype of a spiC mutant is equivalent to that of a secretion component mutant. In addition, translocation of SPI2 effector proteins was shown to require SpiC. Thus, the severe virulence phenotype resulting from deletion of spiC is likely due to the inability to translocate all SPI2 effectors. SpiC was also required to secrete translocon proteins SseB and SseC but not translocated effector SseJ, indicating that lack of assembly of the translocon explains the spiC mutant phenotype.

Animals↗
PubMed2006

Rhesus macaque polyclonal and monoclonal antibodies inhibit simian immunodeficiency virus in the presence of human or autologous rhesus effector cells.

Although antibodies can prevent or modulate lentivirus infections in nonhuman primates, the biological functions of antibody responsible for such effects are not known. We sought to determine the role of antibody-dependent cell-mediated virus inhibition (ADCVI), an antibody function that inhibits virus yield from infected cells in the presence of Fc receptor-bearing effector cells, in preventing or controlling SIVmac251 infection in rhesus macaques (Macaca mulatta). Using CEMx174 cells infected with simian immunodeficiency virus mac251 (SIVmac251), both polyclonal and monoclonal anti-SIV antibodies were capable of potent virus inhibition in the presence of human peripheral blood mononuclear cell (PBMC) effector cells. In the absence of effector cells, virus inhibition was generally very poor. PBMCs from healthy rhesus macaques were also capable of mediating virus inhibition either against SIVmac251-infected CEMx174 cells or against infected, autologous rhesus target cells. We identified both CD14(+) cells and, to a lesser extent, CD8(+) cells as the effector cell population in the rhesus PBMCs. Finally, pooled, nonneutralizing SIV-antibody-positive serum, shown in a previous study to prevent infection of neonatal macaques after oral SIVmac251 challenge, had potent virus-inhibitory activity in the presence of effector cells; intact immunoglobulin G, rather than F(ab')(2), was required for such activity. This is the first demonstration of both humoral and cellular ADCVI functions in the macaque-SIV model. ADCVI activity in nonneutralizing serum that prevents SIV infection suggests that ADCVI may be a protective immune function. Finally, our data underscore the potential importance of Fc-Fc receptor interactions in mediating biological activities of antibody.

Animals↗