Comparison of immune responses to diphtheria and tetanus toxoids of various mouse strains

Immune responses of 11 mouse strains with known genetical characteristics and two outbred strains to diphtheria and to tetanus toxoids were compared. Both diphtheria and tetanus antitoxins were titrated by passive hemagglutination. From the pattern of the immune response, the mouse strains tested may be classified into four groups. [1] Strains ddY (SPF) and ddY (conv) and those with haplotype H-2b, such as C57BL/6 and C57BL/10, were high responders to both toxoids. [2] Strains with H-2d, such as BALB/c, B10.D2 and DBA/2Cr, were intermediate responders to both toxoids. [3] Strains with H-2k, H-2a or, H-2m, such as C3H/He, B10.BR, B10.BR/SgSn, B10.A/SgSnJ and B10.AKM/O1a, were high responders to diphtheria toxoid but low responders to tetanus toxoid. [4] The strain with H-2h4, B10.A (4R), was a poor responder to both toxoids.     

MuMTV antigen expression and mammary tumor incidence in non-inbred dd mice

The expression of mammary tumor virus (MTV) antigen in the milk and various organs of three non-inbred dd mouse stocks (ddO, ddN and ddY) was examined by the immunodiffusion (ID) and micro-immunodiffusion (micro-ID) tests. The rate of MTV antigen expression in the milk was 100% at the first lactation in ddO (6/6) and ddN mice (10/10), and 23% in ddY mice (3/13). Mammary tumor incidence was 13% (mean tumor age: 12.0 months), 32% (9.6 months) and 10% (11.5 months) in ddO, ddN and ddY mice, respectively, In F1 hybrids between MTV-free BALB/c females and dd males, a high level of MTV antigen was detected by the ID test in the milk of (BALB/c X ddO) F1, however, the levels in (BALB/c X ddN) F1 and (BALB/c X ddY) F1 mice were low at the first lactation and elevated with the advance of lactation number. Mammary tumor incidence had a trend to be higher and earlier in these F1 hybrids than in non-inbred dd stocks. The development of mammary tumors and detection of MTV antigen in F1 hybrids indicate the extrachromosomal transmission of MTV by male dd mice. The micro-ID test has shown that the mammary tumors, mammary glands, male genital organs except for the testis and the salivary gland expressed MTV antigen, with a high frequency of suggesting that secondary male genital organs may play an important role in MTV infection in mice.     

Mouse strain-dependent osteoclastogenesis in response to lipopolysaccharide

Bacterial lipopolysaccharide (LPS) is a potent stimulator of bone resorption in periodontitis. Co-culture systems of mouse calvaria-derived osteoblasts and bone marrow-derived preosteoclasts were used as an in vitro osteoclast differentiation. This study revealed that co-cultures using ddY or ICR mouse strain responded differently to LPS while responded equally to 1alpha,25(OH)2D3. Thus, the different response to LPS indicates dissimilarity of two mouse stains in their capacity for generating osteoclasts while the two mouse strains share the similarity in response to 1alpha,25(OH)2D3. To identify which cells between osteoblasts and preosteoclasts in the co-culture are responsible for the dissimilarity, the reciprocal co-cultures were performed between ddY and ICR mouse strains. The treatment of 1,25(OH)2D3 to ddY/ICR (osteoblasts from ddY/preosteoclasts from ICR) and ICR/ddY reciprocal co-cultures also showed the similarity. In case of LPS treatment, the results of ddY/ICR were similar to ddY/ddY and the results of the other reciprocal co-culture, ICR/ddY combination, were consistent with those of ICR/ICR. It suggests that the dissimilarity between the two mouse strains may resident in osteoblasts but not in preosteoclasts. Therefore, the osteoblast is responsible for mouse strain-dependent osteoclastogenesis in response to LPS. Although mouse models will continue to provide insights into molecular mechanisms of osteoclastogenesis, caution should be exercised when using different mouse strains, especially ddY and ICR strains as models for osteoclast differentiation.     

Susceptibility of inbred mouse strains to infection with three species of Metagonimus prevalent in the Republic of Korea

Susceptibility of inbred mouse strains to Metagonimus yokogawai, Metagonimus miyatai, and Metagonimus takahashii infections was studied using BALB/c, ddY, C57BL/6J, C3H/HeN, and A/J mice, with H-2 haplotypes d, s, b, k, and a, respectively. Two hundred metacercariae were orally fed to each mouse, and the worm recovery rates (WRR), worm dimensions, and intrauterine egg numbers were measured at days 3, 7, 14, 21, and 28 postinfection (PI). On day 14 PI, the WRR of M. yokogawai was highest in ddY mice (average, 62.2%); those of M. miyatai and M. takahashii were highest in ddY (19.5%) and BALB/c mice (10.4%), respectively; worm maturation was best in C3H/HeN (M. yokogawai), C57BL/6J (M. miyatai), and ddY mice (M. takahashii). All mouse strains showed higher susceptibility to infection with M. yokogawai than with M. miyatai or M. takahashii. The results show that susceptibility of mice to Metagonimus infection varies according to mouse strain and parasite species but is suggested to be independent of the mouse H-2 haplotype.     

Heligmosomoides polygyrus (=Nematospiroides dubius): the development of self-cure and/or protection in several strains of mice.

Strains of outbred (ICR/CD1 and S--W) and inbred (BALB/C and C57BL/6) mice vaccinated subcutaneously (SQ) with 500, 1,000, or 2,000 exsheathed Heligmosomoides polygyrus larvae developed varying levels of protection upon subsequent oral challenge with larvae. In contrast, the inbred C3H/HEJ strain failed to develop protection at any dosage level tested. ICR/CD1 mice vaccinated intraperitoneally with exsheathed larvae developed a high level of resistance but exhibited extensive adhesions of the viscera. When ensheathed larvae were used for vaccination, ICR/CD1 mice developed a moderate level of protection; but 1% of the vaccine dose was recovered in the intestine as adult stages. Both the inbred and outbred strains given multiple oral infections developed a protection response similar to that strain's response following parenteral vaccination. The specificity of this protection was demonstrated using various complex foreign antigens. In contrast, the self-cure response was observed only in the S--W strain.     

Cryopreservation of mouse spermatozoa in the presence of raffinose and glycerol

When mouse epididymal spermatozoa were rapidly frozen in two steps (37 to -70 degrees C for solid CO2 and -70 to -196 degrees C for liquid nitrogen) as pellets, 18% raffinose provided the greatest protection to ICR mouse spermatozoa against cold-shock; sperm motility and fertilizing ability were 43% and 22.4%, respectively. A small proportion of spermatozoa frozen with 10% sucrose was motile but incapable of fertilizing ovulated oocytes. Glycerol and dimethylsulphoxide were less effective at any concentration examined. However, the fertilizing ability of frozen-thawed ICR spermatozoa was significantly improved (35.5%) by addition of glycerol (1.75% final concentration) to medium containing 18% raffinose. Spermatozoa from one outbred (ddY) and 5 inbred (C57BL/6N, C3H/HeN, DBA/2N, BALB/c and kk) strains of mice were successfully frozen in the presence of 18% raffinose and 1.75% glycerol, although the fertilization rates of frozen-thawed spermatozoa varied among strains (13% for C57BL/6N to 64% for DBA/2N). A small fraction of mouse eggs resulting from fertilization by frozen-thawed spermatozoa developed normally in vitro (37% in C57BL/6N to 71% in ICR) to the blastocyst stage and in vivo (19% for C57BL/6N spermatozoa and ddY oocytes) to Day 18 of gestation.     

Histocompatibility-2 system in wild mice. X. Frequencies of H-2 and Ia antigens in wild mice from Europe and Africa

In this study, data are presented on serologic H-2 typing of 320 wild mice collected in several parts of Europe and Egypt. The sample was typed for 39 class I (K, D) and 16 class II (Ia) antigens. The phenotype frequencies of class I and class II antigens showed high variability in their distribution among different areas, ranging from absence or presence in low frequency in one area to presence in about one-half of the mice in another area. The average phenotypic frequency of class I private antigens was 6.3%; at least 60% of class I alleles (blanks) could not be identified with the available reagents. The data suggest that there might be more than 100 alleles for each class I locus, H-2K and H-2D. The average phenotypic frequencies of Ia-1 private antigens was 10.8%. About 75% of Ia-1 alleles (blanks) could not be identified. The number of Ia-1 alleles was estimated to be in the range of 20 to 50.     

Mutation analysis of left-right axis determining genes in NOD and ICR, strains susceptible to maternal diabetes

BACKGROUND: Genetic background of the fetus contributes to the pathogenesis of congenital malformation after teratogen exposure. Such contribution is illustrated in left-right axis malformations observed in the F1 offspring of nonobese diabetic (NOD) mouse dams and sires from different strains. When sires of the NOD, ICR, or C57BL/6J were mated with NOD dams, incidence varied depending on the fetal genotype, with 65% in NOD x NOD, 24% in NOD x ICR, and 7% in NOD x C57BL/6J. METHODS: As a first step in elucidating the molecular basis of the interstrain differences in susceptibility to situs defects, we compared genomic sequences of six genes HNF3beta, Acvr2b, Nodal, ZIC3, Lefty1, and Smad2, which are involved in the normal development of left-right axis among NOD, ICR, and C57BL/6J strains. RESULTS: The outbred strain ICR had 1) a 0.2-kb insertion in the putative promoter region of the isoform E of HNF3beta together with a G to A change that could create a potential splice acceptor in the exon 3 of HNF3beta (gene frequency P = 0.36), 2) five single base substitutions within the 5' controlling element and a proline to serine substitution (P2S) of Lefty1 (P = 0.77), and 3) a tyrosine to histidine substitution within the prodomain of Nodal (P = 0.48). The inbred strain NOD had the same G to A change as ICR and a three-base deletion in the putative promoter of isoform E of HNF3beta. CONCLUSIONS: We suggest that sequence variations in HNF3beta, Lefty1, and Nodal might account, in part, for the interstrain differences in susceptibility to situs abnormalities among the offspring of diabetic dams.     

Mapping immunodominant antigens and H-2-linked antibody responses in mice urogenitally infected with Chlamydia muridarum

To identify immunodominant antigens and MHC-restricted antibody responses, seven different strains of mice were intravaginally infected with Chlamydia muridarum and compared for antibody responses to 257 C. muridarum proteins. The 7 strains of mice recognized a total of 109 proteins as antigens, of which, 5 antigens (TC0660, TC0727, TC0828, TC0726 & TC0268) were each recognized by 60% or more mice from each mouse strain and thus designated as immunodominant antigens. Furthermore, antibody responses to 19 other antigens displayed strong associations with mouse H-2 haplotypes, including 6 antigens (TC0480, TC0912, TC0229, TCA04, TC0289 & TC0892) whose antibody responses were linked to H-2(b), 8 (TC0035, TC0387, TC0052, TC0781, TC0373, TC0117, TC0066 & TC0396) to H-2(d) and 5 (TC0512, TC0177, TC0589, TC0794 & TC0596) to H-2(k) haplotypes respectively. Interestingly, H-2(b) was negatively associated with antibody responses to most of the antigens that were positively linked to H-2(d) or H-2(k) haplotypes. These results by mapping Chlamydia trachomatis antigens commonly recognized by mice with different strain background and H-2 genes and revealing antigen association with H-2 haplotypes have provided important information for developing chlamydial subunit vaccines and understanding chlamydial pathogenesis.     

Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus. I. Generation and recognition of virus strains and H-2b mutants

Cytotoxic T lymphocytes (CTL) were induced in C57BL/6 and (C57BL/6 X DBA/2)F1 mice after immunization with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV-Arm) and were cloned by limiting dilution in vitro. The cytotoxic activity of these clones was LCMV specific and H-2 restricted. All clones induced in C57BL/6 (H-2b) mice with LCMV-Arm lysed target cells infected with each of five distinct strains of LCMV (Arm, Traub , WE, Pasteur, and UBC ), suggesting recognition of common regions of viral proteins in association with H-2b molecules. In contrast, one clone obtained from (B6 X D2)F1 mice and restricted to the H-2d haplotype only lysed cells infected with one of three strains of virus (Arm, Traub , WE) but not two others (Pasteur, UBC ), suggesting recognition of variable regions of viral proteins in the context of H-2d molecules. To assess the fine specificity for H-2 molecules, we tested H-2Kb-restricted CTL clones for their ability to kill LCMV-infected target cells bearing mutations in their H-2Kb, and we tested clones presumed to be restricted to the H-2Db region for their ability to all LCMV targets cells bearing a mutation in the H-2Db region. Several different patterns of killing of the mutant targets were observed, indicating that a number of different epitopes on the H-2b molecules were used as restricting determinants for LCMV antigen recognition by CTL. Thus, cross-reactive viral determinants were recognized in the context of several different restricting determinants. Mutations in the N or C1 domains of the H-2 molecule affected recognition by a single LCMV specific CTL clone. One implication of this result is that CTL recognize a conformational determinant on the H-2 molecule formed by the association of virus antigen(s) with H-2. An alternate explanation is that one site on the H-2 molecule is involved in the interaction of viral antigens with H-2, whereas another may serve as a binding site for the CTL receptor.     

Susceptibility of five strains of mice to Babesia microti of human origin.

One outbred (CF1) and four inbred (BALB/c, C57, CBA and C3H) strains of mice were tested for susceptibility to Babesia microti of human origin. Of these, intact C3H mice developed higher parasitemia than all other intact mice, while BALB/c mice developed the highest parasitemia among splenectomized mice. Susceptibility was not related to H-2 haplotype in any obvious way. Because C3H and BALB/c mice developed relatively high initial peak parasitemias, the parasite was serially passaged in both of these mouse strains in an attempt to increase parasite virulence. After 30 passages in BALB/c and 49 passages in C3H mice over a period of 12 months, maximum parasitemias were 50 times higher than those observed initially. After the peak parasitemias of these two mouse-adapted parasites had stabilized, the relationship between onset and level of maximum parasitemia and number of parasites inoculated was determined. With both C3H- and BALB/c-adapted parasites, as inoculum size increased, the time required to reach maximum parasitemia decreased and the level of maximum parasitemia increased. Studies involving infection of either mouse strain with parasites adapted to the heterologous mouse strain indicated that C3H mice were more susceptible than BALB/c mice to homologous or heterologous parasites. These data suggest that the virulence of B. microti to the mouse can be increased by prolonged passage in this host. Once adaptation to this host species has occurred, virulence appears to be more dependent on the innate susceptibility of the mouse strain than on adaptation of the parasites to a particular strain of mouse.     

T-cell and antibody typing of a mouse population segregating for Sxr and H-2 haplotype

During investigation of the frequency of recombination of the testis determining gene, Tdy, and the minor histocompatibility antigen gene Hya on the Sxr segment in an outbred mouse stock, we identified two fertile males, one XY and the other XYSxr, which typed H-2k positive using the H-2b anti-H-2k monoclonal antibody HB50, but whose cells failed either to stimulate H-Y specific H-2k restricted T-cell clones, or to be killed by anti-H-2k or anti-H-2k restricted H-Y specific cytotoxic T cells. We investigated these two mice and their existing relatives, using H-2 and H-Y typing methods. The progeny of their test matings with H-2b homozygous C57BL/6 females were also investigated. The results indicate that the transmission of the Hya gene on the Y chromosomes from both mice, and the additional Hya gene on the Sxr segment of the carrier male, allowed for the expression of the H-Y antigen and its detection in the presence of an H-2 haplotype for which we had H-2 restricted H-Y specific typing cells (H-2b and H-2k). Furthermore, we identified the haplotype of the two original males as expressed in the H-2 homozygous and heterozygous F2 progeny as H-2q and discovered an unexpected cross reactivity of the monoclonal anti KkDk antibody HB13 with half the cells of H-2q homozygotes, but not qb heterozygotes.     

Incidence of enteritis of Enterobacteriaceae isolates possessing human colonization factor antigen. New human colonization factors

Of 462 Enterobacteriaceae strains including 435 Escherichia coli isolated from 250 patients, 298 haemagglutinating (HA) cultures were classified into 36 different HA groups. Sixteen of them belonged to Evan's I or II groups, although none possessed CF I or CF II antigen detectable by slide agglutination. Seventy-seven strains showed 4+ mannose resistant (MR) HA with human (53), bovine (2), chicken (6), guinea pig (7) or human and guinea pig (9) erythrocytes. These strains were significantly more frequent in patients under one year of age. Eighty-eight percent of the typable strains belonged to E. coli serogroups O1, O2, O4, O6, O18. HA positivity and fimbrial structures were correlated in 2 isolates (15/1, O18a, c:-K77: H-; 12/2/1 O1: K1: H .). Fimbriae of the two strains exhibited adhesive properties. Their fimbrial antigens differed serologically from each other and from those of the reference strains H 10407 and PB 176. Forty-nine of 4+ human MRHA strains showed variable reactions in the two sera for the new fimbrial antigens.     

T lymphocyte-enriched murine peritoneal exudate cells. III. Inhibition of antigen-induced T lymphocyte Proliferation with anti-Ia antisera.

The recent development of a reliable murine T lymphocyte proliferation assay has facilitated the study of T lymphocyte function in vitro. In this paper, the effect of anti-histocompatibility antisera on the proliferative response was investigated. The continuous presence of anti-Ia antisera in the cultures was found to inhibit the responses to the antigens poly (Glu58 Lys38 Tyr4) [GLT], poly (Tyr, Glu) ploy D,L Ala-poly Lys [(T,G)-A--L], poly (Phe, Glu)-poly D,L Ala-poly Lys [(phi, G)-A--L], lactate dehydrogenase H4, staphylococcal nuclease, and the IgA myeloma protein, TEPC 15. The T lymphocyte proliferative responses to all of these antigens have previously been shown to be under the genetic control of major histocompatibility-linked immune response genes. The anti-Ia antisera were also capable of inhibiting proliferative responses to antigens such as PPD, to which all strains respond. In contrast, antisera directed solely against H-2K or H-2D antigens did not give significant inhibition. Anti-Ia antisera capable of reacting with antigens coded for by genetically defined subregions of the I locus were capable of completely inhibiting the proliferative response. In the two cases studied, GLT and (T,G)-A--L, an Ir gene controlling the T lymphocyte proliferative response to the antigen had been previously mapped to the same subregion as that which coded for the Ia antigens recognized by the blocking antisera. Finally, in F1 hybrids between responder and nonresponder strains, the anti-Ia antisera showed haplotype-specific inhibition. That is, anti-Ia antisera directed against the responder haplotype could completely block the antigen response controlled by Ir genes of that haplotype; anti-Ia antisera directed against Ia antigens of the nonresponder haplotype gave only partial or no inhibition. Since this selective inhibition was reciprocal depending on which antigen was used, it suggested that the mechanism of anti-Ia antisera inhibition was not cell killing or a nonspecific turning off of the cell but rather a blockade of antigen stimulation at the cell surface. Furthermore, the selective inhibition demonstrates a phenotypic linkage between Ir gene products and Ia antigens at the cell surface. These results, coupled with the known genetic linkage of Ir genes and the genes coding for Ia antigens, suggest that Ia antigens are determinants on Ir gene products.     

CTL and serologically defined antigens of B2m,H-3 region

The antigens of the B2m,H-3 region of 13 chromosome 2 congenic strains and seven inbred strains have been studied by using CML and serologic techniques. Nine patterns of cross-reactivity have been defined by CML assays. These results are in agreement with an extend previously described cross-reactivity studies. The reactivities of three monoclonal antibodies previously thought to be reacting with B2M-B are shown to differ: Ly-m11 and J-5 react with cells of strain B10-pa,at and clone 23 does not. Two H-3 region loci are hypothesized on the basis of CML and serologic activity: B2m and H-3. The CTL responses to the B2M antigens are H-2K restricted; the CTL responses to H-3 antigens are H-2D restricted. The restriction of the response to the H-3 antigen requires effector-target identity of the H-2D molecule but not the B2M molecule of the class I antigen. These loci have been separated by recombination from H-42 in the production of the congenic strain B10.FS-a. A gene order of B2m, H-3, H-42 is suggested.     

Strain differences of ether susceptibility in mice

The susceptibility to ether in the following six strains of mice was tested: C57BL/6, DBA/2, BALB/c, C3H/He, ICR and ddY. Mice of 4 weeks old were exposed to a flow of air containing various concentrations of ether for 90 min and the mortalities were assessed. The C57BL/6 strain was the most resistant and the C3H/He strain was the most sensitive to the lethal effect of ether. The susceptibilities of the closed colony mice, ICR and ddY, were intermediate between those of C57BL/6 and C3H/He mice. The DBA/2 and BALB/c strains were more sensitive than these closed colony mice and made up a sensitive group with the C3H/He strain. The LD50 values for ether in male mice of C57BL/6 and C3H/He were 6.0 and 3.1% atm, and in female mice of these strains were 6.6 and 3.2% atm, respectively. The ED50 value of ether which was accompanied by loss of righting reflex after exposure for 10 min was also higher in male C57BL/6 mice than in male C3H/He mice.     

A new histogenetic method for minor histocompatability antigen typing.

A new method for typing minor H antigens is described. The method is based on the observation that effector T cells, sensitized in vivo to minor H mitigens and then rechallenged in vitro, will lyse labeled target cells in the CML assay, provided that the target, the sensitizing, and the responding cells share the same allele at H-2K or H-2D loci. In this method, two congenic lines differing at a minor H locus are cross-immunized (by skin grafting, injection of lymphoid cells, or, preferably, by a combination of both treatments), rechallenged in vitro, and tested against a panel of strains carrying the same H-2 haplotype as the two lines. Target cells of the panel carrying the same minor H antigens as the strain against which the effector cells were sensitized are lysed; target cells not carrying these antigens are unaffected. The feasibility of the method was demonstrated by testing for H-3 antigens of a panel fo H-2b-bearing strains. The new method is faster and more economical than the classicial F1 method which has been used until recently.     

Quantitative variations in the expression of the mouse serum antigen Ss and its sex-limited allotype Slp

A radial immunodiffusion assay for quantitation of the Ss and Slp serum antigens is described. Significant differences between the mean serum concentrations of Ss and Slp were found among various inbred strains. Some of these differences have been shown to be associated with the H-2 haplotype. The quantitative difference between Slp levels associated with the H-2 ^a and H-2 ^S haplotypes has been used as a marker for the S region in the analysis of certain H-2 recombinant strains [A.TH, B10.S(7R), B10.S(9R), and B10.BSVS]. Male mice of two strains with the H-2 ^b haplotype have been shown to have significantly lower levels of Ss compared to males of the other strains tested. Male mice of every strain examined were found to have significantly higher levels of Ss in their serum than females of the same strain. The molecular relationship and developmental patterns of the Ss and Slp antigens have also been investigated using the radial immunodiffusion assay.     

H-2 antigens as genetic markers: a two-dimensional gel electrophoretic study

Direct immunoprecipitation and two-dimensional (2D) gel electrophoresis have been used to identify and characterize genetic variation of the H-2K and H-2D regions. Using inbred strains of mice and alloantisera, haplotype-specific polypeptides were defined for five different H-2 haplotypes. Specific immunoprecipitates prepared from strains of different haplotypes were applied to 2D gels in pairwise combinations to determine whether peptides specific to one haplotype can be distinguished from peptides specific to another. Those haplotype-specific peptides that migrate to unique positions on 2D gels with respect to the positions occupied by haplotype-specific peptides of another haplotype are useful as biochemical genetic markers. Cross-reactivity among K- and D-region antigens of different haplotypes was identified on 2D gels and found to correlate well with existing data based on serological cross-reactivity. An anti-mouse beta 2-microglobulin serum was found to be a useful general reagent for immunoprecipitating haplotype-specific H-2 antigens to permit their visualization on 2D gels.     

Effect of thymocyte-stimulating factor-containing supernatants on the surface antigens of murine thymocytes.

Incubation of murine thymocytes in thymocyte-stimulating factor (TSF)-containing supernatants causes a four- to fivefold increase in the expression of the H-2^k and H-2^d antigens and a similar decrease in the expression of the TL antigen (in TL⁺ strains) on the surface of these cells. Experiments with antisera directed toward the private H-2K and H-2D antigens showed that TSF-containing supernatants cause approximately the same increase in the expression of the H-2K and H-2D antigens of thymocytes of the d and b haplotypes. With thymocytes of the k haplotype, only an increase in the expression of the H-2D antigens takes place, while no significant increase was found for the H-2K antigens. TSF-containing supernatants cause no significant change in the expression of the following antigens on the surface of thymocytes: Thy-1.1, Thy-1.2, Ly-1.2, Ly-2.2, Ly-6.2, Th-B, Ia-1,2,3,7, and G_IX. A factor similar to murine TSF, produced by human peripheral blood leukocytes, does not affect appreciably the expression of the H-2 antigens on the surface of murine thymocytes. The factor(s) causing the increased expression of the H-2 antigens on the surface of murine thymocytes appears to be produced by T lymphocytes. The factor(s) is eluted from a Sephadex G-100 column in at least two broad peaks with molecular weights of 300,000 and 90,000-25,000. Most of the activity enhancing the expression of the H-2 antigens is lost at pH 2, while most of it is maintained at pH 11.5 and at 56 °C. On the basis of these properties, it is concluded that the factor under study is probably different from the factor enhancing the phytohemagglutinin responsiveness of thymocytes.