Adoptive Transfer Of Immunity Research Articles

Adoptive transfer of immunity to hepatitis B virus after T cell–depleted allogeneic bone marrow transplantation

Recipients of allogeneic bone marrow transplantation are pancytopenic for several weeks and immunosuppressed for many months as a result of myeloablative therapy required to eliminate the basic disease and to prevent allograft rejection. After bone marrow transplantation, these patients remain profoundly immunosuppressed by the chemotherapy and immunotherapy used as prophylaxis against graft-vs.-host disease, treatment of established disease or both. These patients are usually dependent on multiple blood products and are therefore at risk for hepatitis B virus infection, which may run a fulminant course. Active immunization against hepatitis B virus in the immediate pre-bone marrow transplantation and post-bone marrow transplantation periods was found to be ineffective, probably because of the absence of T cell-dependent B-cell responses, which persists for approximately 1 yr after bone marrow transplantation. We studied adoptive transfer of immunity to hepatitis B virus through bone marrow transplantation in two populations of patients. The first group (A) consisted of 12 pairs of BMT donors and recipients, in which all bone marrow donors were positive for antibodies to HBc and HBs as a result of previously acquired hepatitis B virus infection and resolution; all recipients were negative to antibodies to HBc and HBs. The second group (B) consisted of eight pairs of donors and recipients in which all the donors were actively immunized against hepatitis B virus before bone marrow transplantation; all recipients were negative for all hepatitis B virus markers. All bone marrow transplantation recipients were monitored for antibodies to hepatitis B virus antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Ablation of persistent hepatitis B by bone marrow transplantation from a hepatitis B-immune donor

Chronic hepatitis B virus (HBV) infection is still a major cause of liver disease for which no definite therapy is available. We describe here a hepatitis B surface antigen (HBsAg) carrier patient with active viral replication (HBV DNA positive) who was treated for leukemia by bone marrow transplantation (BMT) from an HBV immune donor. Following BMT from the antibody to hepatitis B core antigen (anti-HBc) positive/anti-HBs positive bone marrow donor, immune reconstitution of the recipient's bone marrow resulted in clearance of the circulating HBsAg, as well as HBV DNA. The patient acquired immunity against HBV, which lasted for more than 8 months posttransplantation. Therefore, this report provides evidence that adoptive transfer of specific immunity against HBV through allogeneic BMT may lead to clearance of persistent HBV infection. Furthermore, the data support the hypothesis that the HBsAg carrier state is most probably the result of an inefficient immune response against HBV, implying that clearance of HBV may be facilitated by adoptive cellular immunotherapy.

Adoptive transfer of immunity to hepatitis B virus in mice by bone marrow transplantation from immune donors

Recipients of allogeneic bone marrow transplantation are immunosuppressed as a result of their primary disease and by myeloablative therapy. Such patients are dependent on multiple blood products and are at risk for hepatitis B virus infection. Active immunization against hepatitis B in the immediate pre- and post-transplant periods is ineffective, presumably because of decreased T cell-dependent B-cell responses. This study was designed to evaluate, in a mouse model system, the transfer of immunity against hepatitis B to bone marrow transplant recipients through immunization of bone marrow donors against hepatitis B before transplantation. Bone marrow donor BALB/c mice were immunized with a recombinant hepatitis B vaccine. Seroconversion to HBs antibody occurred within 4 wk of primary immunization, and antibody levels in treated donor mice rose above 300 mIU/ml after a single booster injection. Bone marrow recipient mice, conditioned by sublethal irradiation, were injected intravenously with bone marrow cells obtained from syngeneic HBs antibody-positive immune donors. Antibody was detected in 10% of bone marrow recipients within 30 days of transplantation and in 56% 1 mo after a booster injection that led to a secondary rise in HBs antibody. Adoptive transfer of immunity to hepatitis B also occurred after transplantation of T cell-depleted bone marrow cells from hepatitis B-immune donors, albeit at a lower HBs antibody level. These results indicate that immunity to hepatitis B can be transferred in mice by bone marrow transplantation from hepatitis B-immune donors to immunosuppressed recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adoptive transfer of immunity to hepatitis B virus in mice by bone marrow transplantation from immune donors

Recipients of allogeneic bone marrow transplantation are immunosuppressed as a result of their primary disease and by myeloablative therapy. Such patients are dependent on multiple blood products and are at risk for hepatitis B virus infection. Active immunization against hepatitis B in the immediate pre- and post-transplant periods is ineffective, pre- sumably because of decreased T cell–dependent B-cell responses. This study was designed to evaluate, in a mouse model system, the transfer of immunity against hepatitis B to bone marrow transplant recipients through immunization of bone marrow donors against hepatitis B before transplantation. Bone marrow donor BALB/c mice were immunized with a recombinant hepatitis B vaccine. Seroconversion to HBs antibody occurred within 4 wk of primary immunization, and antibody levels in treated donor mice rose above 300 mIU/ml after a single booster injection. Bone marrow recipient mice, conditioned by sublethal irradiation, were injected intravenously with bone marrow cells obtained from syngeneic HBs antibody–positive immune donors. Antibody was detected in 10% of bone marrow recipients within 30 days of transplantation and in 56% 1 mo after a booster injection that led to a secondary rise in HBs antibody. Adoptive transfer of immunity to hepatitis B also occurred after transplantation of T cell–depleted bone marrow cells from hepatitis B–immune donors, albeit at a lower HBs antibody level. These results indicate that immunity to hepatitis B can be transferred in mice by bone marrow transplantation from hepatitis B–immune donors to immunosuppressed recipients. Furthermore, such bone marrow transplant recipients were able to respond to a booster immunization, suggesting secondary immune response in bone marrow recipients after primary response in donors. These data support the rationale for active vaccination of potential human bone marrow donors against hepatitis B, followed by booster vaccination to bone marrow recipients. (HEPATOLOGY 1993;17:955–959.)

Tumour rejection after adoptive transfer of line-10-immune spleen cells is mediated by two T cell subpopulations.

The growth of line-10 tumours in naive guinea pigs is prevented by adoptive transfer of spleen cells that are hyperimmune to this hepatocellular carcinoma. To study the T cell subpopulations responsible for the adoptive transfer of immunity, various cell populations were removed from immune spleen cells using monoclonal antibodies (mAbs) and magnetic microspheres. Spleen cell subpopulations were identified by mAb after flow cytometry and rosette formation with the magnetic microspheres. mAb CT5 was confirmed to be a pan T cell marker, while the CT6 (anti-T-suppressor/cytotoxic) and CT7 (anti-T-cell) markers were present on two different T cell subpopulations. So our results show that CT7 mAb cannot be used as a pan T cell marker as was published previously. Moreover, the mAb H155 (anti-T-helper/inducer) reacted with the same T cell subpopulation recognized by CT7. So we designated this H155/CT7-positive subpopulation as T helper/inducer cells. Removal of the CT6-, CT7-, or the H155-positive T cells from the immune spleen cells resulted in loss of the in vitro proliferative response to line-10 tumour protein and tuberculin purified protein derivative (PPD). The H155/CT7 (anti-T-helper/inducer)-positive spleen cells did not express MHC class II antigens as determined by mAb 25E3. In most experiments, elimination of MHC-class-II-positive cells did not change the in vitro proliferative response to line-10 protein, whereas the response to tuberculin PPD was completely abrogated. Immune spleen cells after depletion of CT6-, CT7- or H155-positive cells, failed to transfer immunity. However, after depletion of MHC-class-II-antigen-positive cells the line-10 immunity was still present, whereas the immune response to tuberculin PPD was lost. In conclusion, our data indicate that immunity to the line-10 tumour is the result of a cooperation between at least two different T cell subpopulations, the T helper/inducer (CT7/H155) cells and the T suppressor/cytotoxic cells (CT6). If this is a common feature, then the therapeutic approach of in vitro expanded TIL cells should take into consideration the requirement of two T cell subsets.

Vaccination of Lewis rats with temperature-sensitive mutants of Mycoplasma pulmonis: adoptive transfer of immunity by spleen cells but not by sera

Temperature-sensitive mutant vaccines protect rats against Mycoplasma pulmonis infection. The role of the humoral or cellular immune response in resistance to mycoplasma infection was investigated by adoptive-transfer experiments. Spleen cells from Lewis rats vaccinated but not challenged with wild-type organisms (vaccinated) and spleen cells from rats vaccinated (or not) and challenged were effective in preventing syngeneic recipients from developing respiratory disease. There was also a significant reduction in the incidence and number of challenging organisms in the respiratory system. In contrast, sera from the same donors had no detectable effect on the number of mycoplasmas recovered or on lesion development in the respiratory tract. We conclude that cellular immunity rather than humoral immunity generated in vaccinated rats confers protection against subsequent infection.

Hymenolepis nana: Adoptive transfer of protective immunity and delayed type hypersensitivity response with mesenteric lymph node cells in mice

A marked degree of footpad swelling was observed in BALB/c mice infected with Hymenolepis nana eggs, when soluble egg antigen was injected into their footpads 4 to 21 days after the egg infection, indicating delayed type hypersensitivity responses in infected mice. Adoptive transfer with mesenteric lymph node cells from donor mice ( BALB c strain; +/+) infected with eggs 4 days before cell collection could confer this hypersensitivity to recipient nude mice (BALB/c strain; nu/nu). These mesenteric lymph node cells were then divided into two fractions, blastenriched and blast-depleted cells, by density gradient centrifugation with Percoll. The recipients intravenously injected with the blast-depleted cell fraction showed a marked increase in footpad thickness, whereas the intravenous transfer of the blast-enriched cell fraction resulted in an insignificant increase in footpad thickness. The transfer of the blastenriched cell fraction, but not of the blast-depleted cell fraction, conferred a strong adoptive immunity on syngeneic recipient nude mice, when the immunity transferred was assessed by examining cysticercoids developed in the intestinal villi on Day 4 of challenge infection. The lack of delayed type hypersensitivity response in mice that received the blast-enriched cell population was not due to a lack of the capacity of the cells to induce the response, because the cells were capable of inducing a significant increase in thickness of footpads of normal mice when these cells were locally injected into the footpad together with soluble egg antigen. Furthermore, experiments involving passive transfer and preferential localization of radiolabeled cell populations suggested that footpad swelling could be induced by a very small proportion of sensitized migratory lymphocytes, while at least a significant number of sensitized blast lymphocytes is required for the rejection of cysticercoids in the intestine.

Intraintestinal migration to the epithelium of protective, dividing, anti-Trichinella spiralis CD4+ OX22- cells requires MHC class II compatibility.

Abstract We have measured the intraintestinal migration of activated Th cells belonging to the OX8- OX22- and OX8- OX22+ subsets derived from thoracic duct lymph of rats infected with Trichinella spiralis. Cells in S-phase were labeled with 125I-UdR or 3H-TdR in vitro and transfused i.v. Identical proportions of both helper cell subsets localized in the small intestine but three to four times as many OX22- cells as OX22+ cells migrated to the intestinal epithelium. Experiments using MHC class I and II recombinant rats indicated that localization of OX8- OX22- cells in the lower lamina propria (LP) and muscularis was reduced by 50% in MHC class II incompatible rats as assessed by total gamma-counts but by a factor of three when labeled cells were counted. Movement of labeled OX8- OX22- cells to the epithelium was reduced by a factor of five to seven when assessed by the same methods. Quantitative cellular localization in the gut and further movement to the epithelium were normal in class I-mismatched rats. The movement from the lower-mid LP to the epithelium was undertaken principally by dividing cells as indicated by a progressive loss of grain counts in labeled cells and the appearance of doublet-cells in mitosis. In allogeneic combinations, extravasating cells remained localized close to their primary site of exit in the muscularis and lower-mid LP. The results suggest that the requirement for MHC class II compatibility for adoptive transfer of immunity in rats to T. spiralis is functionally related to localization of the protective OX22- cell subset in the epithelium.

Expression of systemic protection and delayed-type hypersensitivity to Listeria monocytogenes is mediated by different T-cell subsets

The relationship between acquired cellular resistance and delayed-type hypersensitivity (DTH) during the immune response to Listeria monocytogenes was investigated. Treatment of concanavalin A-stimulated Listeria-immune spleen cells with anti-CD8 antibody plus complement abrogated the adoptive transfer of systemic antilisterial immunity but had no effect on the transfer of DTH. In contrast, in vitro depletion of the CD4+ T-cell subset eliminated the ability of culture-activated cells to transfer DTH reactivity but did not interfere with the adoptive transfer of protection. In vivo, the infusion of anti-CD8 antibody inhibited the expression of both actively and adoptively transferred protection but did not influence the development of DTH skin test reactivity to L. monocytogenes antigens. In vivo depletion of the CD4+ T-cell subset eradicated the DTH response, with only minor influence of the protective anti-Listeria response. The apparent functional dissociation of the CD4+ (DTH) and CD8+ (protection) T-cell populations was further emphasized by our findings that the adoptive transfer of protection was dependent on a cyclophosphamide-sensitive cell population, whereas DTH reactivity was mediated by a cyclophosphamide-resistant population.

MHC-unrestricted transfer of antilisterial immunity by freshly isolated immune CD8 spleen cells.

Immune CD8 cells, which play an essential role in the adoptive transfer of antilisterial immunity, can specifically lyse Listeria-bearing macrophages in vitro in an MHC-unrestricted manner. In contrast, the adoptive transfer of immunity by unseparated immune lymphocytes has been reported to be MHC-restricted. To address the restriction properties of CD8 effectors in vivo, we assessed their efficacy in protecting syngeneic and allogeneic recipients. Protection was determined by comparing the number of viable splenic Listeria in naive mice and in recipients of 60 million CD8-enriched, L3T4-depleted, Listeria-immune spleen cells, 2 days after the infusion of 10,000 Listeria. Donor cells from B6 (H-2b) mice transferred about 4 logs of protection in syngeneic recipients and more than 2 logs in allogeneic B10.A (H-2a) or B10.BR (H-2k) mice. Immune B10.A CD8 cells transferred equivalent protection to B6 mice. Protection was almost completely abrogated by the lysis or lethal irradiation of CD8 cells before transfer in vivo. On the other hand, the depletion of macrophages or NK cells did not impair adoptive transfer. By comparison, nonimmune CD8 cells from normal mice or from mice stimulated with an irrelevant Ag in vivo did not transfer substantial immunity to allogeneic recipients. We have noted previously that protective CD8 cells inhibit phagocyte accumulation in the spleen of Listeria-infected syngeneic recipients. In the present studies, we observed similar changes in adoptively immunized allogeneic mice. Reduced phagocyte accumulation may reflect Listeria-dependent lysis of infected phagocytes by immune CD8 cells. In support of this, we showed that Listeria-immune donor cells rapidly acquired the capacity to mediate Listeria-dependent, MHC-unrestricted lysis of macrophages after incubation with small amounts of IL-2 in vitro. In sum, our data establish that Listeria-immune CD8 cells can function in vivo in MHC incompatible hosts, and indirectly support the hypothesis that the destruction of infected phagocytes may be important in T cell-mediated immunity against Listeria and perhaps other intracellular pathogens.

Immunity to coccidiosis: T-cell control of infection with Eimeria vermiformis in mice does not require co-operation with inflammatory cells.

The necessity for co-operation between lymphocytes and myeloid-derived inflammatory cells in the mediation of anti-coccidial immunity was investigated using mice infected with Eimeria vermiformis. Reciprocal exchange of immune lymphocytes between H-2 compatible strains of contrasting susceptibility to infection (resistant BALB/B and susceptible C57BL/10) resulted in successful transfer of immunity in both homologous and heterologous exchanges. Recipients of immune cells, whatever their original response phenotype, expressed a high degree of immunity to infection, indicating that the differential susceptibility of the strains is a property of their lymphoid cells and is not attributable to their capacity to mount inflammatory responses. This conclusion was confirmed by the successful adoptive transfer of immunity into NIH mice previously exposed to 600 rad X-irradiation; at this level of irradiation inflammatory responsiveness is severely depressed. Additional confirmation that strain-response phenotype is lymphocyte dependent and that immune lymphocytes can mediate their effects against E. vermiformis without the intervention of inflammatory cells was obtained from studies on the mucosal mast cell response to infection. No correlation existed between the development of intestinal mastocytosis, an index of T-cell-mediated inflammatory responsiveness, and the expression of resistance to E. vermiformis in BALB/c (resistant), C57BL/10 (susceptible) and NIH (susceptible) mice.

Transfer Factor: Past, Present and Future

Adoptive transfer of cell-mediated immunity to specific antigens in humans was first demonstrated by Lawrence (1) in 1949, thus opening a new avenue of research that has led both to increased understanding of basic immune mechanisms and to the development of immunomodulation therapy. Law­ rence originally showed that transfer of whole viable lymphocytes from a normal tuberculin skin test-positive donor to a normal skin test-negative recipient resulted in a conversion of the recipient to skin-test positivity, but this observation created little interest in the immunologic community for several reasons. In 1955, the lymphocyte was mentioned for the first time as a possible immunologic organ. Traditionally, the lymphocyte had been studied in hematologic rather than in immunologic terms . In the third edition of his classic textbook on the anatomy of the lymphoid system, Professor A. Joffy of the University of Bristol proposed three questions to lymphocytes: Where do you come from, where do you go and what do you do, if anything? In 1962(2) , 1. Miller showed that the immune system in chickens could be divided into two components , namely the B lymphocyte derived from the bursal system (B cell) producing antibodies that protect against infection from microorganisms (pneumococcus , meningococcus, streptococcus, gonococ­ cus, etc) and thymic-dependent (T cell) systems that protect against fungi, parasites , viruses, mycobacteria, and cancer metastases . Previously, Law­ rence (3) demonstrated that delayed cutaneous hypersensitivity (DH) respon­ siveness could also be transferred by soluble extracts of leukocytes

Experimental syphilis in guinea pig.

The infrequent use of guinea pig in experimental syphilis, the not well genetically and immunologically characterized strains of animals originating from places with unspecified conditions of husbandry, and the various strains of Treponema pallidum used for infection provided inconsistent and discouraging results. For eight decades the rabbit has been the major animal model in studies of syphilis. However, the lack of readily available inbred strains of rabbits--necessary for adoptive transfer experiments--has been a stumbling block in revealing the mechanisms responsible for immunity, susceptibility, and resistance to T. pallidum infection. These difficulties have recently been overcome by demonstration of inbred strains susceptible to T. pallidum infection, paving the way to studies of adoptive immunity. The guinea pig may also be a better model than the rabbit for immunomanipulations (irradiation, injection with antibodies specific to various cell populations), allowing a closer insight into the immunopathologic mechanism operating during the course of syphilitic infection. The "rediscovery" of the guinea pig as a model for experimental syphilis and recent years of intensive studies justify a review summarizing older data and providing the most recent information. The authors, having first-hand experience with this model, will provide detailed information on (1) historical background; (2) course of infection with T. pallidum in inbred and outbred strains of guinea pigs; (3) the ID50 for various strains; (4) various routes of infection; (5) age and sex-dependent susceptibility to infection; (6) kinetic of the humoral response to specific and non-specific treponemal antigens; (7) appearance of autoantibodies and immune complexes; (8) cellular response, including lymphoproliferative response, macrophage inhibitory factor(s) production, chemotaxis and adoptive transfer of immunity by purified T cells; and (9) a complete list of references.

Mediation of immunity to Eimeria vermiformis in mice by L3T4+ T cells.

Immunity to infection with Eimeria vermiformis was transferred in NIH mice by both the nylon wool-adherent (B-cell-enriched) and nonadherent (T-cell-enriched) fractions of lymphocytes (spleen and mesenteric lymph node) taken from infected donors. Transfer was more variable with the adherent fraction, and when contaminating T cells were removed by treatment with anti-Thy1 monoclonal antibody (MAb) and complement, this fraction lost all protective activity. The protective effect of T-cell-enriched populations of mesenteric lymphocytes was abrogated by treatment with anti-L3T4 MAb and complement in vitro before transfer or by opsonization with this MAb in vitro before intravenous inoculation into recipients. Similar treatments of cells with anti-Lyt2 MAb did not have this effect, confirming that Thy1+ L3T4+ cells mediate the adoptive transfer of immunity to E. vermiformis. Thy1+ L3T4+ cells were also shown to limit the replication of E. vermiformis in primary infections: mice depleted of this subset (by thymectomy followed by intravenous injection of anti-L3T4 MAb) passed greater numbers of oocysts over a longer period of time than did mice similarly depleted of Lyt2+ cells.

Learning and memory deficits associated with autoimmunity: Significance in aging and Alzheimer's disease

AbstractThis review focuses on the significance of brain‐reactive antibodies (BRA) to ageassociated cognitive decline and Alzheimerapos;s disease, drawing on evidence available from both human and animal studies. Human studies suggest a relationship between BRA formation, age, and Alzheimerapos;s disease. Experiments with mice indicate that BRA formation and age‐related learning deficits are accelerated following adoptive transfer of immunity from aged to young mice. Furthermore, mice selected for autoimmunity and early formation of BRA also show accelerated, age‐related learning deficits. It is concluded that a further analysis of the nature of BRA and their targets within the nervous system could reveal important immunological influences in cognitive dysfunctions related to aging and Alzheimerapos;s disease. It is suggested that treatments that delay or prevent age‐related immunological dysfunctions be evaluated for their ability to retard age‐associated cognitive decline.

Theileria sergenti感染牛に対する耐過牛白血球の移入効果

Theileria sergenti感染牛に対する耐過牛白血球の移入効果

Immunity to coccidiosis: adoptive transfer in NIH mice challenged with Eimeria vermiformis.

The development of a reliable model for the adoptive transfer of immunity to coccidiosis (infection with Eimeria vermiformis in NIH mice) is described. More than 10(8) of a mixture of spleen and mesenteric lymph node (MLN) cells, given either intravenously or intraperitoneally, were required to transfer a significant degree of protection. Dividing cells, present in the donors at 10 or 14 days after priming, but not at 5 or 19 days, were shown to be the effectors. When examined separately, MLN cells were found to be superior to spleen cells, and the injection of as few as 5 x 10(7) was capable of substantially reducing the oocyst output from a challenge inoculum. The recipients of cells from primed mice had earlier, and sometimes higher, titres of specific antibodies in the serum but, overall, there was no correlation between these titres and protection. Further characterization of the cells responsible for adoptively transferring immunity to this infection should now be possible.

Adoptive transfer of immunity to Treponema pallidum Nichols infection in inbred strain 2 and C4D guinea pigs.

T lymphocytes purified from lymph nodes and spleens of chancre-immune, inbred strain 2 guinea pigs, when infused into syngeneic guinea pigs, conferred protection against challenge with Treponema pallidum subsp. pallidum Nichols. No protection was conferred by similar injections of cell suspensions from normal guinea pigs or guinea pigs immunized with T. phagedenis biotype Reiter or T. pallidum-free testis supernatants from infected rabbits. Similar results were obtained with homozygous C4D guinea pigs. After several months of infection, 2 of 11 strain 2 and 1 of 8 strain C4D recipients of T. pallidum-immune cells developed an erythematous reaction of short duration at the injection site; 2 of these recipients were positive for T. pallidum. Throughout the experimental period the humoral response to treponemal antigens was substantially lower in the adoptively immune guinea pigs than in various unprotected control groups. Passive immunity to infection with T. pallidum, however, seems to be dose related, since asymptomatic infection persisted for as long as 3 months after challenge in strain 2 guinea pigs transfused with 10(8) T. pallidum-immune lymphocytes, but not in C4D recipients of twice as many immune cells.

Adoptive transfer of immunity to Listeria monocytogenes. The influence of in vitro stimulation on lymphocyte subset requirements.

BALB/c mice develop specific and relatively long lasting immunity after exposure to sublethal numbers of viable Listeria monocytogenes. This immunity can be passively transferred to naive recipients with maximal protection conferred by spleen cells obtained from donors 6 days after immunization. Immunity that can be directly transferred to syngeneic recipients is surprisingly short lived. Cell recipients lose immunity as early as 72 hr after transfer, and recipients express no detectable immunity after 1 wk. This short lived immunity requires both L3T4+ and Lyt-2+ T cell populations for full expression. Both the level of immunity transferred and the duration of the protective response expressed in recipients are dramatically increased if the spleen cell population is cultured in vitro with concanavalin A before cell transfer. Recipients of concanavalin A-activated cells express antigen-specific levels of immunity increased 100- to 1000-fold compared with syngeneic recipients of directly transferred immune spleen cells. In addition, this elevated level of adoptively transferred immunity remains constant for at least 8 wk. Transfer of this culture-enhanced immunity requires only an Lyt-2+ T cell population and is not influenced by cells of the L3T4+T cell subpopulation. Both direct as well as culture-enhanced transfer of immunity require major histocompatibility complex-compatible recipients. These findings suggest that two phenotypically distinct T cell subpopulations function in the development of the immune response to L. monocytogenes and that only one cell subpopulation is required for expression of immunity to this intracellular parasite.

Regeneration of humoral immunity to herpes simplex virus following T-cell-depleted allogeneic bone marrow transplantation.

We investigated the adoptive transfer of immunity to herpes simplex virus (HSV) in 61 recipients of T-cell-depleted marrow allografts. Up to 3 months after bone marrow transplantation (BMT), high titres of HSV antibody (Ab) are passively acquired from blood products. This antibody has a half-life of 40.3 days, so that determination of recipient immunity to HSV cannot be made during the early post-transplant period. By 4 months after the allograft, seronegative recipients of seronegative donors had near-background levels of HSV Ab. Seropositive recipients, whether they were excreting virus or not, had high titres of HSV Ab regardless of donor status. Surprisingly, the seronegative recipients of HSV seropositive donors remained seronegative, a result at variance with observations made in the recipients allografts from which T-cells had not been removed. Thus, T-cell depletion modifies the adoptive transfer of humoral immunity to HSV, and an immune donor alone no longer ensures continued antibody production in the recipient.