IL-2 production, IL-2 receptor expression, and IL-2 responsiveness of spleen and mesenteric lymph node cells from inbred mice infected with Trichinella spiralis

The in vitro production of IL-2 and IL-2R expression by lymphoid cells of inbred mice of strong (NFS), intermediate (C3H), or weak (B10.BR) in phenotype of Trichinella spiralis (TS) rejection was measured during a primary infection. Maximum production of IL-2 by spleen and mesenteric lymph node (MLN) cells occurred at 5 days postinfection. Cell depletion experiments demonstrated that Lyt-1.2+ T cells were predominantly responsible for in vitro IL-2 production. Cells from strong-responder NFS mice produced more IL-2 than cells from intermediate-responder C3H or weak-responder B10.BR mice. Similarly, after TS infection, NFS mice had significantly more IL-2R expressing MLN cells than B10.BR or C3H MLN cells. All mouse strains displayed a dose-dependent increase in in vitro IL-2 production after infection with 100 to 800 TS. This effect was most pronounced in NFS mice. Limiting dilution analysis of day 5 infected MLN cells demonstrated that the frequency of TS-reactive CD4+ cells was threefold higher in NFS mice than B10.BR and fourfold higher than in C3H mice. Finally, MLN cells taken from infected NFS mice responded to an exogenous source of IL-2, whereas MLN cells from infected C3H or B10.BR mice were unable to do so. We conclude that strong responsiveness in parasite rejection may be related to the amount of IL-2 produced as well as to the capacity of the lymphocytes of each mouse strain to respond to IL-2. Although these differences help explain the strong rejection phenotype of NFS mice, they fail to separate C3H and B10.BR mice where TS-responsive CD4+ precursors, IL-2 production, and dose responsiveness are all lower for the intermediate phenotype (worm rejection) C3H than the weak phenotype B10.BR mice.     

Genetic analysis of the relationship between interleukin production and worm rejection in Trichinella spiralis-infected inbred mice

The production of interleukin 1 (IL-1), IL-2, and IL-3 by peritoneal macrophages, mesenteric lymph node (MLN), or spleen cells from inbred strains of mice infected with Trichinella spiralis was examined. The mice belonged to the worm rejection phenotypes previously characterized as strong (NFS), intermediate (C3H, BUB, DBA/1, SWR, CBA, etc.), or weak (B10.Q, B10.BR, etc.). Strong responder NFS mice produced approximately twice as much IL-1 as intermediate responder C3Heb/Fe or weak responder B10.BR mice. IL-3 production varied slightly among strains but did not show any relationship to the phenotype of rejection (highest: C3Heb/Fe, B10.BR; lowest: B10.Q). Of 16 strains of inbred mice and 6 F1 hybrid crosses assessed, marked variations occurred in IL-2 production from MLN cells in response to T. spiralis antigen challenge in vitro. When 16 mouse strains were compared IL-2 production ranged from 5.1 units/ml (A/J) to 29.8 (NFS). Variations in IL-2 production among mouse strains did not relate directly to MHC haplotype, and the capacity of an individual strain to release IL-2 or IL-3 did not correlate with adult worm rejection phenotype. Genetic linkage studies proved that the gene(s) regulating IL-2 production in T. spiralis infection were not linked to the gene(s) regulating adult worm rejection. Regression analysis showed a weak correlation of high IL-2 production with weak worm rejection suggesting that IL-2 production or an associated process is a negative factor in primary worm rejection.     

Cryptosporidium parvum infection in mice: inability of lymphoid cells or culture supernatants to transfer protection from resistant adults to susceptible infants

The ability of murine lymphoid cells or culture supernatant fractions to transfer protection against Cryptosporidium parvum was examined. Spleen or mesenteric lymph node (MLN) cells were taken from adult mice resistant to C. parvum and given either directly or following in vitro culture to infant mice. Neither spleen or MLN cells, nor cells or supernatant fractions from in vitro cultures transferred protection from resistant adult donors to susceptible infant recipients. These results may be due to limitations in the present model. Alternatively, the resistance of infant mice to C. parvum may not be immunologically mediated.     

AKR/J gene(s) unlinked to H-2 determines dominant inheritance of lymphocyte hyporesponsiveness to acetylcholine receptor

Mice with the H-2b major histocompatibility complex haplotype are high immune responders to nicotinic acetylcholine receptors (AChR), whereas mice with the H-2k haplotype are generally low responders. F1 progeny of C57BL/6 (H-2b) mice crossed with mice of most H-2k strains are high responders to AChR in standard conditions of testing helper T cell proliferation in vitro (4 X 10(5) lymph node cells/microwell, 1 wk after primary challenge in vivo). In contrast, the F1 progeny of AKR/J (H-2k) crossed with high responder (H-2b) strains (B6, A.BY, or C3H.SW) were all hyporesponsive to AChR when lymphocytes were tested at 4 X 10(5) cells/well. However, at a density of 1 X 10(6) or greater/well, a high level of antigen-specific responsiveness was demonstrable in the F1 hybrid lymphocytes. A shift from low to high responsiveness to AChR at high cell densities was observed also in the H-2b strain AKR.B6. Other strains previously demonstrated to be low responders to AChR did not become responsive to AChR when lymphocyte numbers were increased to 1.4 X 10(6)/well. The N2 generation yielded by backcrossing (AKR X B6)F1 mice to AKR/J were all low responders, whereas N2 progeny derived by backcrossing F1 to B6 were high or low responders in a ratio of approximately 1:1 (independent of their H-2 phenotype). Results consistent with this observation were obtained in (AKR X B6) F2 mice. These data suggest that at least one AKR/J gene outside of the H-2 complex exerts a hyporesponsive influence on the I-A-dependent helper T cell response to AChR in H-2b mice.     

Blast cell activity in mice infected with Hymenolepis nana, H. diminuta and Trichinella spiralis: in vivo uptake of 125IUdR in lymphoid tissues and gut

The kinetics of the lymphoblast response in mice during the course of a primary infection with Hymenolepis nana was measured by the in vivo uptake of 125IUdR. The response was most marked in tissues local to the site of infection, involving the nodes draining the small intestine but not other areas, e.g., inguinal lymph nodes. A close correlation between these responses and the course of infection was observed. Uptake of 125IUdR was greatest in the mesenteric lymph node (MLN) but the peak reached in this organ was later than that in Peyer's patches (PP), small intestine (SI) and spleen (S). The increase in lymphoblast activity of the MLN was similar with Trichinella spiralis; no significant blast cell response to infection with H. diminuta was found till day 9 after injection, the results being similar to those obtained when H. nana infections were established using cysticercoids rather than eggs. It has been shown that the increase in lymphoblast activity was closely correlated with the presence of cells which are most effective in adoptive transfer immunity. A dose-dependent effect was detected in blast cell activity of MLN in different infection levels with T. spiralis and H. nana.     

Induction of oncofetal antigen-specific suppressor pathways, involving Thy-1+ cells, during the early stages of tumor progression

The early stages of tumor progression were modelled by intraperitoneally injecting BALB/c mice daily with exponentially increasing numbers of mitomycin C-treated, syngeneic MPC-11 tumor cells. At various stages of this regime, mesenteric lymph node (MLN) and spleen cells were assessed for regulatory activity on the induction of cytotoxic T lymphocytes (CTL) in vitro. Cells present in both MLN and spleens of mice whose daily tumor dose had reached 102,400 MPC-11 cells impaired the generation of CTL specific for MPC-11 and specific for oncofetal antigen(s) shared between MPC-11 and Day 14-15 syngeneic fetal liver cells. Depletion of Thy-1+ cells from the regulatory cell populations removed the suppressive activity. The regulatory cells did not affect the induction of CTL specific for H-2b antigens in the context of H-2d (i.e., BALB/c) class I MHC.     

Heligmosomoides polygyrus: decreased apoptosis in fast responder FVB mice during infection

Primary infection with Heligmosomoides polygyrus in some strains of mice is chronic although fast responder mouse strains eliminate the parasite in a short period of time. The reason for the differences is unknown. In this study apoptosis, proliferation, IL-2 and IL-6 production of mesenteric lymph node (MLN) and spleen cells in vitro from fast (FVB) and slow (C57Bl/6) responder mice were compared during H. polygyrus infection. FVB cells showed decreased apoptosis, more proliferation and more cytokine production than cells from C57Bl/6 mice during infection. At the beginning of infection in C57Bl/6 mice the apoptosis of CD4(+) but not CD8(+) cells significantly increased in MLN and spleen cell cultures. Apoptosis, when the first immune signal is given by infective larvae, might play an important role in the modulation of the response in slow responder mice.     

Suppression of antigen-specific interleukin 2 production in the MRL/MpJ-lpr/lpr mouse

Several murine strains with spontaneously occurring systemic lupus erythematosus-like disease demonstrate defects in immunoregulation. The MRL/MpJ-lpr/lpr (MRL-1) strain develops a severe age-progressive defect in interleukin 2 (IL 2) production in response to mitogen or antigen. In this study, we demonstrate in vitro the presence of suppressor cells in the lymph nodes of naive mice of the MRL background. Suppression by MRL-1 lymph node cells was partially reversed by treatment with anti-Lyt-1.2 monoclonal antibody and complement and was moderately radiosensitive. Suppression by lymph node cells from the congenic MRL/MpJ-+/+ (MRL-+) mouse was somewhat more resistant to treatment with anti-Lyt-1.2 and complement, or radiation. Lymph node cells from the H-2-syngeneic mouse strain, C3H/HeJ, failed to suppress. Thus, lymph nodes from mice of the MRL background contain cells capable of suppressing in vitro IL 2 responses. We next performed cell transfers to determine whether suppressor cells contribute in vivo to the IL 2 defect. Lymph node cells, but not spleen cells, from MRL-1 mice by 5 to 6 mo of age suppressed antigen-specific IL 2, CTL, and DTH responses when transferred into young MRL-+ recipients. Transfer of identical numbers of lymph node cells from age-matched MRL-+ mice failed to suppress IL 2 production. Transfer of suppression was sensitive to treatment with monoclonal anti-Lyt-2.1 and complement, and to 250 rad of radiation. Thus, this study suggests a role for active suppression of IL 2 production in the establishment of the IL 2 defect in the MRL-1 mouse. Further, suppression may involve phenotypically distinct T lymphocyte subpopulations.     

The intestinal mast cell response to Trichinella spiralis infection in mast cell-deficient w/wv mice

The intestinal mast cell response and lymphoblast activity, as measured by the incorporation of 3H-thymidine into mesenteric lymph node cells (MLN) of WBB6F1-w/wv(w/wv) mice, their normal congenic littermates (+/+) and C57BL/6J mice, were compared after infection with Trichinella spiralis. Marked and similar blast cell activity and an increase in number of cells were observed in the MLN of infected w/wv and C57BL/6J mice 7 and 15 days P.I. In contrast to C57BL/6J mice, primary T. spiralis intestinal infections were prolonged in w/wv mice and more muscle larvae were recovered from w/wv mice 29 days post-infection. In C57BL/6J mice mucosal mast cell (MMC) numbers increased on day 7 P.I. whereas in w/wv mice these cells did not increase significantly until day 15 post-infection, reaching a peak on day 22. In w/wv mice, the response to secondary infection as determined by an accelerated expulsion of adult worms did not occur until day 11 postchallenge whereas in +/+ and C57BL/6J mice worm expulsion was nearly complete at that time. In both primary and secondary infections, the MMC numbers in w/wv mice were significantly lower than in C57BL/6J or +/+ mice. The results suggest that prolongation of T. spiralis infection in w/wv mice is associated with delayed appearance of mast cells in the intestinal mucosa which may reflect slow generation of the intestinal inflammatory response.     

Lymphocytes from H2 mice produce lower levels of several cytokines than congenic H2 or H2 mice

Inbred mice of congenic strains that differ only in their H2 haplotype were used to examine the effects of MHC genes on production of cytokines. Spleen and lymph node cells were stimulated with mitogens in vitro, and cytokine protein was assessed by ELISA and/or bioassays. Cells from H2b mice synthesized less IL-3, IL-4, IL-5, TNF and IL-10 (less clearly) than the equivalent cells from H2k or H2d mice. Production of IL-6 by H2b spleen and lymph node cells was lower than that by cells from H2d mice. In addition, lower lymphoproliferative responses were observed in lymph node cultures from H2b mice. These effects were evident in congenic B10 and BALB strains. B10 H2b mice stimulated in vivo with anti-CD3 had lower levels of IFN-gamma and IL-5 protein in their serum compared with equivalent H2k and H2d mice. Because class I- or II-mediated antigen presentation was not required in our model, an immunoregulatory gene in the central MHC is implicated. Preliminary studies of MHC recombinant mice suggested that the gene or genes responsible lie telomeric of IEbeta. Evidence that the H2b haplotype carries an immunoregulatory allele with a small but consistent effect on cytokine production warrants further investigation.     

Evidence for differential induction of helper T cell subsets during Trichinella spiralis infection

The H-2-compatible mouse strains, AKR and B10.BR, exhibit disparate responses to infection with the parasitic nematode Trichinella spiralis. The resistant AKR mice expel intestinal adult worms faster than susceptible B10.BR mice. We tested antibody and lymphokine responses in these strains. With respect to antibody responses, the B10.BR mice had 3- to 10-fold more serum IgE and T. spiralis-specific IgG1 and IgA than AKR mice. The B10.BR mice also had greater numbers of IgG and IgA plaque-forming cells than AKR mice. In contrast, AKR mice produced T. spiralis-specific IgG2a, whereas the B10.BR mice did not. The antibody response kinetics of these strains were similar. We also analyzed lymphokine secretion after restimulating lymphocytes in vitro with T. spiralis Ag. The AKR mesenteric lymph node cells produced more IFN-gamma and less IL-4 than the B10.BR mesenteric lymph node cells. The B10.BR splenocytes produced more IL-4 than the AKR splenocytes, although splenocyte IFN-gamma production was not different. The kinetics of IL-4 production also differed between the two strains. In summary, resistant AKR mice produced more IFN-gamma and T. spiralis-specific IgG2a than susceptible B10.BR mice, which produced more IL-4, IgE, and T. spiralis-specific IgG1. Our results are consistent with differential activation of Th cell subsets in T. spiralis-infected AKR and B10.BR mice.     

Trichinella spiralis infections of inbred mice: immunologically specific responses induced by different Trichinella isolates

The immune response of inbred mice was studied following infection with Trichinella spiralis var. pseudospiralis (TP) or with isolates of T. spiralis derived from a pig or from an arctic fox. Animals given a primary infection with 1 isolate of Trichinella and challenged 21 days later with the same or different isolates responded more quickly by expelling worms from the homologous challenge. In addition, although mesenteric lymph node cells from mice infected with each isolate of Trichinella would proliferate in vitro when cultured with antigen derived from each of the others, the strongest proliferation response always occurred when cells were cultured in the presence of antigen prepared from the specific isolate used to infect the mouse from which the cells were derived. In addition, it was possible to prepare monoclonal antibodies that recognized an antigen expressed by TP which was not shared by T. spiralis isolates and vice versa. Collectively, these data support the conclusion that the differences observed in the kinetics of immune responsiveness to different Trichinella isolates are referable, at least in part, to differences among the isolates in the expression of functionally relevant antigens.     

A survey of susceptibility to infection with Trichinella spiralis of inbred mouse strains sharing common H-2 alleles but different genetic backgrounds

Twenty-eight different inbred strains of mice representing five different H-2 haplotypes were compared for degree of susceptibility to a primary infection with Trichinella spiralis. Marked differences in susceptibility, measured by the average number of muscle larvae per host, were seen among strains of mice sharing common H-2 alleles. The genes controlling these differences must therefore map at loci outside the major histocompatibility complex. Strains of mice sharing the H-2k haplotype were generally more susceptible than strains expressing other haplotypes and strains expressing H-2q alleles were most resistant. Strains of mice were ranked in order of decreasing susceptibility. Knowledge of these ranking may be of value to researchers wishing to select strains of mice appropriate for studies on T. spiralis.     

T-helper-1 and T-helper-2 immune responses in mice infected with the intestinal fluke Neodiplostomum seoulense: their possible roles in worm expulsion and host fatality

Neodiplostomum seoulense is highly pathogenic and lethal to experimental mice; most worms are expelled within 2 mo of acquisition. In this study, T-helper (Th) cell immune responses were studied in N. seoulense-infected BALB/c mice. Spleen and mesenteric lymph node (MLN) cells of infected mice proliferated in response to parasite antigens; CD4+ T cells proliferated more than CD8+ T cells. Antigen-induced interferon (IFN)-gamma (a Th1 cytokine) secretion began to increase at day 7 postinfection (PI) in spleen and MLN cells, and this was maintained at day 28 PI, whereas interleukin (IL)-4 (a Th2 cytokine) secretion was somewhat lower. Similar results were observed for mRNA signals of IFN-gamma and IL-4. Antigen-specific serum total immunoglobulin (Ig)G, IgG1, IgM, and IgA levels (Th2-induced) were elevated from days 7 to 14 to day 28 PI, and IgG2a (Th1-induced) was elevated at days 21 to 28 PI. Interestingly, the numbers of macrophages (Th1- or Th2-induced), which were found to kill N. seoulense worms in vitro, increased remarkably during days 14-28 PI in spleens and small intestines of infected mice. This study shows that mixed Th1 and Th2 responses occur during the course of N. seoulense infection in BALB/c mice. Heavy infiltrations of macrophages in the small intestine may participate in host damage and worm expulsion.     

Immune sensitization to syngeneic organ-specific intestinal antigens in the Lewis rat

In human chronic inflammatory bowel disease involving mucosal epithelium, sera and lamina propria mononuclear cells are reactive with cell surface components isolated from gut epithelial cells. To define a model system in which the disease-inducing potential of such immune factors could be rigorously evaluated, we sought to immunologically sensitize inbred murine strains to syngeneic colonic epithelial cell-associated components (ECAC-C), to define precise in vivo and in vitro conditions to optimize ECAC-C reactivity, and to initially explore whether such cells could elicit tissue injury in epithelium after adoptive transfer to naive animals. Following footpad immunization, Day 42 lymph node cells but not splenocytes were reactive with syngeneic ECAC-C, as shown by a linear increase in [3H]thymidine incorporation over a wide range of antigen concentration (0.5 to 100 micrograms/ml). A subsequent 48-hr exposure to ECAC-C and/or interleukin 2 resulted in a more restricted responsiveness, proliferation occurring only in the presence of ECAC-C or mitogen and not to a coimmunogen (PPD). Further evidence that lymph node cells from ECAC-C/CFA immunized animals were indeed sensitized to syngeneic ECAC-C included ability of donor animals to mount highly significant earlobe DTH responses to ECAC-C, indicating the presence of antigen-specific T-DTH cells, and the failure of polymyxin B, in doses sufficient to inhibit LPS-induced mitogenesis, to reduce lymph node cell responsiveness to ECAC-C, known to be contaminated with LPS. ECAC-C-specific circulating antibody and T-cytotoxic cells were not detected. Adoptive transfer of Day 42 lymph node cells, sensitized in vivo and conditioned in vitro, was not associated with tissue injury in syngeneic recipients in preliminary experiments. This model system, with antigen-specific cells analogous to those present in diseased mucosa of human chronic inflammatory bowel disease, may be an important means to determine the pathophysiologic significance of anti-epithelial cell immune responses in these disorders.     

Genetic control of immune responses to the 18-kDa protein of Mycobacterium leprae. Different TH1 subsets may be involved in proliferative and delayed-type hypersensitivity responses.

In vitro and in vivo responses to the 18-kDa protein of Mycobacterium leprae have been analysed in different strains of mice. Lymphocytes from BALB/cJ (H-2d), BALB.B (H-2b), B10.BR (H-2k), and B10.M (H-2f) mice primed with 18-kDa protein yielded high T cell proliferative responses, while those from C57BL/10J (H-2b) mice yielded lower responses. Both H-2 and non-H-2 genes contributed to the magnitude of responsiveness. F1 mice from high and low responder strains showed high responsiveness to the 18-kDa protein. Supernatants from lymph node cell cultures prepared from 18-kDa protein-immunised BALB/cJ, B10.BR, and C57BL/10J mice contained IL-2 but no IL-4, indicating that activated T cells from both high and low responder mice were of a TH1 phenotype. Cell cultures from low responder C57BL/10J mice produced less IL-2 than those from high responders. The low responsiveness to the 18-kDa protein in proliferative assays might be due to a low frequency of antigen-specific T cells in the C57BL/10J mouse strain. BALB/cJ, C57BL/10J, and F1 (BALB/cJ x B10.BR) mouse strains were tested for in vivo DTH reactions to the 18-kDa protein. All strains, including C57BL/10J, were high DTH responders. Although DTH effector cells and 18-kDa protein-specific proliferative T cells belong to the TH1 subset, our data comparing high and low responder status indicate that distinct TH1 subpopulations are stimulated in response to the 18-kDa protein of M. leprae.     

Genetic control of experimental autoimmune myasthenia gravis in mice. I. Lymphocyte proliferative response to acetylcholine receptors is under H-2-linked Ir gene control.

As a first step in determining the genetic control of experimental autoimmune myasthenia gravis in mice, we tested the proliferative responses of lymph node cells to torpedo acetylcholine receptors (TAR). Studies with congenic and recombinant inbred strains of mice revealed that T-cell responses to TAR are controlled by an H-2 linked Ir gene, mapping in the I-A subregion of mouse major histocompatibility complex.     

4-Hydroxy-3-nitrophenyl (NP) acetyl-hapten specific lymphocyte proliferation. I. Mice bearing Igh-1b allotype can cross-react with 4-hydroxy-5-iodo-3-nitrophenyl (NIP) acetyl hapten

Hapten specific T cell proliferation was induced in several strains of mice. When lymph node T cells from 4-hydroxy-3-nitrophenyl acetyl-keyhole lympet hemocyanin (NP-KLH)-primed mice were stimulated in vitro with NP-polymer glutamic acid-lysine-phenyl alanine (NP-GL phi) or NP-ovalbumin (NP-OVA), they displayed a good level of proliferative responses. It was observed that NP-GL phi could induce NP-hapten specific proliferation even with NP-KLH lymphocytes from GL phi nonresponder strains. NP-KLH primed lymphocytes from C57BL/6 (H-2b, Igh-1b), CKB (H-2k, Igh-1b), CWB (H-2b, Igh-1b), and B10.BR (H-2k, Igh-1b) mice showed good proliferative responses to both 4-hydroxy-5-iodo-3-nitrophenyl (NIP) acetyl-GL phi and NIP-OVA antigens. However, NP-KLH primed lymphocytes from C3H/He (H-2k, Igh-1j) and C3H. SW (H-2b, Igh-1j) mice displayed poor proliferative responses to NIP-GL phi and NIP-OVA antigen. These results suggested that the gene coding for the NIP-cross-reaction might be mapped in the Ig heavy-chain linked locus.     

Myelin proteolipid protein-induced experimental allergic encephalomyelitis. Variations of disease expression in different strains of mice

Strains of mice with diverse genetic backgrounds were tested for susceptibility to experimental allergic encephalomyelitis (EAE) induced by myelin proteolipid protein. EAE was elicited in all strains of mice tested, but the clinical and histologic features varied. SJL (H-2s) mice had a high incidence of both clinical and histologic disease characterized by early onset of clinical signs. Inguinal lymph node T cells from diseased animals responded specifically [( 3H]thymidine incorporation) to proteolipid protein and not to myelin basic protein. In contrast, BALB/c (H-2d), DBA/1 (H-2q), C57BL/6 (H-2b), AKR (H-2k), CBA (H-2k), C3H (H-2k), B10.BR (H-2k), and C57BR (H-2k) mice showed a later onset of clinical signs and typically a lower disease incidence. However, the most marked variations in disease incidence occurred among BALB/c (H-2d) substrains in which the incidence of EAE ranged from eight of nine (BALB/cPt) to complete resistance (BALB/cWt and BALB/cORNL). Because these BALB/c substrains were initially derived from the same inbred genetic source and are serologically identical at H-2, these results suggest that expression of proteolipid protein-induced EAE in the mouse involves additional loci outside the MHC.     

Trichinella spiralis: role of non-H-2 genes in resistance to primary infection in mice

Two strains of mice which share identical H-2 genes but differ in their genetic backgrounds were compared for their ability to resist infection with Trichinella spiralis. The two strains of mice, C3HeB/FeJ and AKR/J, share the H-2k haplotype which is associated with susceptibility to primary infection with T. spiralis in H-2 congenic strains of mice. AKR/J mice, infected with 150 infective muscle larvae, harbored significantly fewer muscle larvae 30 days postinfection than did mice of the strain C3HeB/FeJ. Approximately equal numbers of worms establish in the small intestine of AKR and C3H mice, but the AKR mice expelled adult worms from the gut more rapidly than did mice of the C3H strain. By Day 9 postinfection, 50% of the worms had been expelled by the AKR mice whereas expulsion of worms from C3H mice was delayed beyond Day 9 and occurred primarily between Days 10 and 12. Over this same experimental period (Days 6-12), fecundity of female worms from AKR mice, measured as the mean newborn larvae/female/hour, was approximately one-half that of worms taken from C3H mice. These results support the conclusion that genes outside of the mouse H-2 complex regulate expulsion of adult worms from the gut. These background genes also markedly influence the fecundity of female worms.