Age‐associated increase in the expression of T cell antigen receptor γ chain genes in mice

Abstract

T cell function generally declines with age. To determine the underlying cause of the age-related decline, we compared the expression levels of T cell antigen receptor genes encoding gamma, beta and alpha chains in the lymphoid tissues of young (8 wk old) vs. aged (40 wk old) mice. An age-associated increase in gamma chain gene transcripts was evident in the thymocytes, spleen cells and mesenteric lymph node cells. Aged mice had a relatively high proportion of CD3+CD4-CD8- cells but a reduced level of CD3+CD4-CD8+ cells in the lymphoid tissues, as compared with young counterparts. The allo-reactivity in the lymphoid cells, as assessed by mixed lymphocyte reaction (MLR) responses, decreased with advancing age. On the contrary, increased levels of syngeneic MLR and spontaneous cytolytic activity were noted in the lymphoid cells of aged mice, as compared with findings in their young counterparts. A remarkable increase in the number of CD3+CD4-CD8- cells and level of the gamma chain gene messages was also detected in the responder cells of day 4 syngeneic MLR culture from aged mice. An increase in the number of T cells bearing gamma chain may be related to the alterations in immunological functions in aged mice.

Deletion of Mls‐reactive T cells in H‐2‐compatible but Mls‐incompatible bone marrow chimeras

“…Responder spleen cells (5 x lo5) were cultured with 5 x lo5 irradiated (3300 rad) stimulator spleen cells in 0. agreement with our previous report [12], the thymocytes on day 21 expressed abundant level of a and @ chain gene transcripts, whereas the spleen cells at this time expressed a relatively high level of y chain gene transcripts but a small amount of a and p chain mRNA. A normal level of a and fl chain gene transcripts was finally detected in the spleen on day 56 after reconstitution ( Fig.…”

“…Recently, Marrack et al have directly shown that I-E on BM-derived cells is sufficient to induce clonal elimination of Vgl7a T cells capable of recognizing I-E molecules [ll]. We have previously reported that sequential appearance of the thymocyte subpopulations and TcR gene messages occurred during proliferation and differentiation of donor-derived T cell precursors in thymus of irradiated mice at the early stage after BM transplantation [12]. The use of radiation BM chimeras may provide a pertinent approach for investigating T cell differentiation in adult mice.…”

A novel CD3‐ J11d+ subset of CD4+CD8‐ cells repopulating thymus in radiation bone marrow chimeras

“…As consistent with our previous report [19,241, the first cells that repopulate thymus were derived from radioresistant thymocytes of the host. Donor-derived Thy-1.2' cells were first detected on day 8 and an almost complete replacement from Thy-1.1' cells to Thy-1.2' cells occurred by day 21 (Fig.…”

“…The double-negative thymocytes have been found to be highly heterogeneous [12][13][14][15][16]. In addition, CD8 single-positive cells contain CD8+CD3-Jlld-cells that are immediate precursors of double-positive thymocytes [17, 181. We have previously reported that thymocyte subpopulations appeared at the early stage in whole body-irradiated bone marrow (BM) chimeras in a sequential manner similar to that seen in fetal thymus [19]. The use of thymocytes at early stage in BM chimera provides a pertinent source for understanding lineage relationships of each T cell subset in adult thymus.…”

Predominant appearance of γ/δ T lymphocytes in the liver of mice after birth

“…A high level of liver y/6 Tcells (up to 40% of MNC) was observed in old nude mice. An age-related increase of y/6 TcR mRNA was reported in the spleen of nude mice, and the possibility of extrathymic differentiation of y/6 T cells in nude mice has already been proposed [45,46]. In addition to the high level of co-expression (-40%) of CD8 antigens on y/6 Tcells in the liver of normal C3H/HeN mice, y/6 Tcells in the liver of athymic mice also expressed the CD8 antigens (-70%).…”