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In flow microfluorometry analysis of thymus and lymph node cells of C57BL/6(I-E-,Mlsb) mice rendered neonatally tolerant to (C57BL/6 × AKR/J)F1 (I-E+,Mlsb/a) lymphoid cells, both CD4+ and CD8+ cells showed a striking reduction in the number of Vβ6+ cells capable of recognizing Mlsa in the context of major histocompatibility complex (MHC) class II molecules, indicating that clonal deletion of Vβ6+ cells by Mlsa antigen occurs just at a stage of immature Vβ6lowCD4+CD8+thymocytes. On the other hand, the number of Vβ11+ cells capable of recognizing I-E was markedly reduced in CD4+ cells, but CD8+ cells showed only partial (20%) reduction of such a population. The clonal deletion of Vβ11+ cells by I-E may begin at the transitional stage from Vβ11lowCD4+CD8+ to Vβ11highCD4+CD8- single-position cells, and Vβ11lowCD4+CD8+ cells differentiating to Vβ11highCD4-CD8+ cells seem to be resistant to clonal deletion. Vβ11+ T cells are also stimulated by staphylococcal enterotoxin A (SEA) irrespective of expression of CD4 or CD8. Nearly all of both Vβ11+CD4+ and Vβ11+CD8+ lymph node T cells were deleted by the injection of SEA every other day from birth. In their thymi, both Vβ11+CD4+CD8- and Vβ11+CD4 CD8+ single-positive thymocytes were deleted, and the proportion of Vβ11low thymocytes was lower than that of normal mice. The clonal deletion of Vβ11+ T cells by SEA injection occurs at a stage of immature Vβ11lowCD4+CD8+ double-positive thymocytes, resulting in deletion of both Vβ11+CD4+ and Vβ11+CD8+ T cells. [ABSTRACT FROM AUTHOR]

We have previously reported that T-cell receptor (TcR) γδ-bearing T cells precede TcR αβ-bearing T cells in appearance in the thymus after whole-body irradiation. In the present study, the kinetics of appearance of intestinal intra-epithelial lymphocytes (IEL) was examined in mice after whole-body irradiation with a lethal dose of 9.5 Gy or with a sublethal dose of 6 Gy. The number of CD3+ IEL decreased to the lowest value 4 days after irradiation with 9.5 Gy, and thereafter increased to half as many as the normal level by day 7. Thy-1+TcRαβ- IEL and Thy-TcRβ IEL recovered considerably by day 7 after the irradiation, whereas Thy-1+TcRαβ+ IEL and Thy-1+TcRαβ+ IEL hardly recovered at this stage. All mice died within 12 days after irradiation with a lethal dose of 9.5 Gy. On the other hand, when irradiation dose was decreased to 6 Gy, all mice survived beyond 40 days after irradiation. The number of CD3+ IEL recovered to the normal level by 10 days after irradiation with 6 Gy. Consistently with the results in mice irradiated with a lethal dose, the first cells to increase in IEL of mice irradiated with a sublethal dose were TcRγδ+ IEL expressing Thy-1 antigen. The number of Thy-1+TcRγδ+ IEL increased to approximately two-fold as many as that in normal mice by day 10, while TcRαβ+ IEL began to increase in number from day 20 after irradiation and recovered to the normal level by day 40 after irradiation. Thus, sequential appearance of TcRγδ+ and TcRαβ+ IEL was evident after irradiation, similar to that seen in the thymus after irradiation. The IEL on day 10 after sublethal irradiation, which is composed mainly of Thy-1+TcRγδ+ IEL, exhibited a strong cytolytic activity against P815 in the presence of anti-CD3 mAb, suggesting that the early appearing Thy-1+TcRγδ+ IEL may play important roles in epithelial immunity at an early stage after irradiation. [ABSTRACT FROM AUTHOR]

Murine thymocytes are divided into four major populations on the basis of expression of CD4 and CD8 antigens. The bulk of evidence favours the view that CD4-CD8- cells can develop into CD4-CD8+ and CD4+CD8- cells via the CD4+CD8+ stage in the thymus. However, CD4-CD8+ and CD4+CD8- thymocyte subsets contain not only CD3+ mature cells but also CD3- immature cells, which seem to be intermediate cells between CD4-CD8- and CD4+CD8+ cells. Here we demonstrate mouse strain differences in the proportion of immature single-positive thymocyte subsets in thymus at the steady or developing state. In C3H mice, immature CD4+ CD8- is dominant in proportion over CD4-CD8+ in foetal thymus and in donor-derived thymocytes at an early stage of bone marrow transplantation. On the other hand, immature CD4 CD8+ is dominant over CD4+CD8- during T-cell development in the case of B10.BR mice. An intermediate pattern was shown in the case of Fi mice. Both of these immature single-positive subsets gave rise to doublepositive cells after 24 hr culture. These results suggest that there exist two distinct differential pathways; one is from CD4- CD8- cells to CD4+ CD8+ cells via CD4-CD8+ cells, and another is via CD4+CD8- cells, and that an application of the 'CD8 pathway' or 'CD4 pathway' seems to be genetically destined by BM-derived cells but not by thymic stromal cells. [ABSTRACT FROM AUTHOR]

In order to search for a possible role of abnormally proliferating T cells in developing autoimmune disease in lpr mice, and to define the difference of the T ceils among various lpr-congeneic mice with different clinicopathological findings, the T-cell receptor (TcR) Vβ gene expression in the enlarged lymph nodes (LN) of C3H/HeJ-lpr/lpr (C3H-lpr), C57BL/6-1pr/lpr (B6-lpr) and MRL/Mp-lpr/lpr (MRL-lpr) mice was analysed. A RNA blot analysis using several Vβ-specific probes showed that the Vβ3 gene, whose products are important for recognizing Mlsb/a, was used in B6-lpr and MRL-lpr with the Mlsb/b but not in C3H-lpr with the Mlsb/a. The Vβ5 gene, which is selectively related to I-E molecules, was predominantly used in B6-lpr(I-E-) but not in C3H-lpr(I-E+) nor MRL-lpr(I-E+). Similarly, the V12 gene was also expressed in B6-lpr but not in C3H-lpr. To compare in detail the Vβ repertoire among lpr mice with different major histocompatibility complex (MHC) backgrounds, the Vβ gene sequences in the cDNA libraries from LN cells of C3H-lpr were analysed, following the recent investigation of B6-lpr mice (Ohga et al., 1989). Eleven β-chain cDNA out of 32 β cDNA in B6-lpr and 24 β-chain cDNA out of 55 β cDNA in C3H-lpr were found to contain sequences with open reading frames that potentially encode functional TcR β-chain. The fequencies of the messages in the cDNA libraries from these mice were consistent with the RNA blot analysis using Vβ3- and Vβ5-specific probes. It was notable that 36% of the functional β-chain mRNA in B6-lpr and 50% of the β mRNA in C3H-lpr expressed the Vβ8 gene family. When the TcR Vβ gene expression was compared between the LN cells in C3H-lpr, B6-lpr and MRL-lpr, as reported by Singer et al. (1986), the usage of Vβ genes other than the Vβ8 gene family in B6-lpr (H-2b) LN cells differed significantly from those in C3H-lpr (H-2k) and MRL-lpr(H-2k). The results presented here indicate that the usage of Vβ genes is heavily influenced by the genetic background of lpr mice, similar to normal mice, but with preferential usage of the Vβ8 gene family as a common structural feature in lpr gene-induced cell populations. [ABSTRACT FROM AUTHOR]

We have previously shown that extrathymic rearrangements of T-cell receptor (TcR) γ and δ chain genes occur in the peripheral lymphoid tissues of athymic nude mice. To further determine where the TcR gene rearrangements occur in nude mice, we investigated the rearrangement and expression of the TcR genes in the long-term cultured bone marrow (LTBM) cells which were homogenous in developments without mature T cells as assessed by FACS analysis. The LTBM derived from euthymic mice contained IcR γ and δ chain genes in germline configuration, while gene rearrangements of both locus were detected in the LTBM cells from nude mice. These results suggested that γ and δ gene rearrangements do occur in the bone marrow cells of nude mice and that the T-call precursors in bone marrow may be increased in frequency in such animals. [ABSTRACT FROM AUTHOR]

Delayed footpad reactions and acquired cellular resistance to Listeria monocytogenes were studied in mice whose mononuclear phagocyte system (MPS) had been blocked or stimulated. Colloidal carbon was used for the blockade of MPS and Corynebacterium parrum used for the stimulation. Strong delayed footpad reactions. On the other hand, the i.v. rejection of 3 × 101; listeria induced an appreciable level mice, while in MPS-stimulated mice, i.v. injection with even 4 × 103; listeria could not induce such strong delayed footpad reaction. On the other hand, the i.v. injection of 3 × 10¹ listeria induced an appreciable level of delayed footpad reaction only in MPS-blocked mice. Acquired cellular resistance was depressed by MPS stimulation, whereas it was augmented by MPS blockade. These results suggested that non-specific activity of MPS modulates subsequent immune responses after inoculation of listeria. [ABSTRACT FROM AUTHOR]

The delayed footpad reaction to sheep erythrocytes (SRBC) was studied in mice whose mononuclear phagocyte system (MPS) was blocked or stimulated. Colloidal carbon or carrageenan was used for the blockade of MPS and Corynebacterium parvurn or diethylstilbestrol used for the stimulation. The optimal dose of SRBC for the induction of the delayed footpad reaction was lower in MPS-blocked mice than in non-treated mice, whereas a high dose of SRBC was required for the induction of the strongest delayed footpad reaction in MPS-stimulated mice. These results suggest that non-specific phagocytic function of MPS modulates subsequent immune responses after administration of antigens. [ABSTRACT FROM AUTHOR]