Ontogenic development and tissue distribution of V gamma 1-expressing gamma/delta T lymphocytes in normal mice.

Among T cell subsets, γδ T cells uniquely display an Ag receptor-based tissue distribution, but what defines their preferential homing and homeostasis is unknown. To address this question, we studied the resources that control γδ T cell homeostasis in secondary lymphoid organs. We found that γδ and αβ T cells are controlled by partially overlapping resources, because acute homeostatic proliferation of γδ T cells was inhibited by an intact αβ T cell compartment, and both populations were dependent on IL-7 and IL-15. Significantly, to undergo acute homeostatic proliferation, γδ T cells also required their own depletion. Thus, γδ T cell homeostasis is maintained by trophic cytokines commonly used by other types of lymphoid cells, as well as by additional, as yet unidentified, γδ-specific factors.

Section: Discussionmentioning

confidence: 99%

γδ T Cell Homeostasis Is Controlled by IL-7 and IL-15 Together with Subset-Specific Factors

Baccalà

Witherden

Gonzalez-Quintial

et al. 2005

“…In WT mice, V␥1 ϩ T cells are a major ␥␦ T cell subset in the spleen (20 -50%) and among iIELs (15-30%) (39). The effect of V␥1 ϩ T cell deficiency on the splenic and IEL ␥␦ T cell repertoires was assessed by comparing the distribution and number of ␥␦ T cells between adult WT and V␥1 Ϫ/Ϫ mice.…”

Section: Resultsmentioning

confidence: 99%

Delineation of the Function of a Major γδ T Cell Subset during Infection

Andrew

Newton

Dalton

et al. 2005

γδ T cells play important but poorly defined roles in pathogen-induced immune responses and in preventing chronic inflammation and pathology. A major obstacle to defining their function is establishing the degree of functional redundancy and heterogeneity among γδ T cells. Using mice deficient in Vγ1+ T cells which are a major component of the γδ T cell response to microbial infection, a specific immunoregulatory role for Vγ1+ T cells in macrophage and γδ T cell homeostasis during infection has been established. By contrast, Vγ1+ T cells play no significant role in pathogen containment or eradication and cannot protect mice from immune-mediated pathology. Pathogen-elicited Vγ1+ T cells also display different functional characteristics at different stages of the host response to infection that involves unique and different populations of Vγ1+ T cells. These findings, therefore, identify distinct and nonoverlapping roles for γδ T cell subsets in infection and establish the complexity and adaptability of a single population of γδ T cells in the host response to infection that is not predetermined, but is, instead, shaped by environmental factors.

“…It has been shown that TCR␥␦ i-IEL mainly use V␥7, V␥1, and V␥2 (33)(34)(35). To examine TCR repertoire of the TCR␥␦ i-IEL restored by enforced expression of Bcl-2 in an IL-15-deficient environment, we compared the V gene expressions of TCR␥␦ i-IEL of Bcl-2 Tg, IL-15 KO, Bcl-2 Tg ϫ IL-15 KO and control WT mice.…”

Section: V␥ and V␦ Gene Expression By The Rescued Tcr␥␦ I-iel In Bcl-mentioning

confidence: 99%

Enforced Expression of Bcl-2 Partially Restores Cell Numbers but Not Functions of TCRγδ Intestinal Intraepithelial T Lymphocytes in IL-15-Deficient Mice

Nakazato

Yamada

Yajima

et al. 2007

IL-15 knockout (KO) mice have severely reduced numbers of TCRγδ intestinal intraepithelial T lymphocytes (i-IEL), suggesting requirements of IL-15 signaling in the development or maintenance of i-IEL. To determine an involvement of survival signals via Bcl-2 in IL-15-mediated homeostasis of TCRγδ i-IEL, we introduced a bcl-2 transgene into IL-15 KO mice. In situ apoptosis of TCRγδ i-IEL was decreased in Bcl-2 transgenic (Tg) × IL-15 KO mice compared with IL-15 KO mice. The enforced expression of Bcl-2 partially restored the numbers of TCRγδ i-IEL in IL-15 KO mice. However, effector functions of TCRγδ i-IEL, including cytokine production and cytotoxic activity, were not recovered in Bcl-2 Tg × IL-15 KO mice. Importantly, TCRγδ i-IEL in Bcl-2 Tg × IL-15 KO mice expressed a reduced level of eomesodermin, a transcription factor critical for effector functions of NK cells and CD8+ T cells. Similar to the case of TCRγδ i-IEL, enforced expression of Bcl-2 restored the numbers but not the functions of NK cells in IL-15 KO mice. These results suggest that Bcl-2-mediated survival signal is involved in the IL-15-mediated homeostasis of TCRγδ i-IEL and NK cells, but other signals from IL-15 are critical for inducing transcription factors, such as eomesodermin for their effector functions.