Human T cell activation. IV. T cell activation and proliferation via the early activation antigen EA 1.

Nakamura, Shuji; Sung, S.-S. J.; Bjorndahl, Jay M.; Fu, Shu Man

doi:10.1084/jem.169.3.677

Cited by 61 publications

(20 citation statements)

References 22 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…47 Activated Ras plays a central role for cell-surface expression, 48 which reaches a maximum at 18 to 24 hours after stimulation. 49,50 Although the function of CD69 has not been ultimately defined, cross-linking studies have demonstrated a role for CD69 in regulating the production of T-cell activating cytokines such as IL-2 51 as well as the IL-2 receptor (CD25), 52 interferon ␥, and tumor necrosis factor-␣. 53 Among other alterations of the cytokine network observed after TCD therapy, 3,54 a decrease of IL-2 production 36,37,55 as well as of transcription examined on a single-cell basis 56 may be of particular relevance to the disturbed T-cell function.…”

Section: Discussionmentioning

confidence: 99%

Defective T-helper cell function after T-cell–depleting therapy affecting naive and memory populations

Heitger

Winklehner

Obexer

et al. 2002

Blood

View full text Add to dashboard Cite

IntroductionSevere immune dysfunction is a predictable consequence of high-dose anticancer chemotherapy with or without autologous or allogeneic stem cell support and results in significant morbidity and mortality in potentially curable diseases. [1][2][3] One obvious explanation for such immune dysfunction is a depletion of immune cells by the cytotoxic effects of anticancer drugs. 4,5 However, even after quantitative regeneration immune cells do not regain full immune competence for a prolonged period of time. [6][7][8][9][10] T cells play a key role in multiple immune responses. Therefore, both a depletion and a disturbed function caused by cytotoxic anticancer treatment are potentially harmful to the immune surveillance of the host, including an increased susceptibility to infections with otherwise less harmful pathogens. [11][12][13][14][15] T-cell reconstitution after cytotoxic therapy does not repeat fetal T-cell ontogeny. [16][17][18][19] In fact, the first T cells that repopulate the host after T-cell depleting (TCD) therapy expand extrathymically from peripheral residual T cells whereas a thymus-dependent T-cell regeneration is delayed and may be even incomplete in adult patients in whom thymic function has declined. [20][21][22] Extrathymically expanded T cells bear a memory phenotype, 23 as their expansion is determined by antigenic stimulation. 24 Their capacity to restore full T-cell function is believed to be limited, because of (1) skewing of the T-cell repertoire 25-27 and (2) an increased susceptibility to apoptosis, including activation-induced apoptosis. 28 In contrast, T cells with a naive phenotype presumably represent recent thymic emigrants, 23,[29][30][31] having matured from precursors via thymopoiesis, and thus may be spared from the postchemotherapy immune dysfunction.To test this hypothesis we investigated by flow cytometry the in vitro immune function of distinct naive (CD4 ϩ CD45RA ϩ ) and memory (CD4 ϩ CD45RA Ϫ ) T-helper cells. Examinations were performed at one to 3 months after completion of TCD therapy, a time point at which CD4 ϩ CD45RA ϩ T cells were readily detectable but not yet fully recovered.Upon stimulation with polyclonal mitogens in vitro we found a reduced up-regulation of the early activation-induced cell surface molecule, CD69, detectable in CD4 ϩ T cells even in the presence of exogenous interleukin 2 (IL-2). Strikingly, CD4 ϩ CD45RA ϩ cells were similarly affected as CD4 ϩ CD45RA Ϫ cells by decreased stimulatory responses and an increased susceptibility to apoptosis as detected by annexin V staining. 32,33 When peripheral blood mononuclear cell (PBMC) populations were enriched for T cells, the stimulatory responses improved markedly. Together, the findings are consistent with a concept that factors external to T cells, eventually affecting T-helper cells irrespective of a naive or memory phenotype, contribute to the prevailing T-cell dysfunction in the early post-TCD therapy period. Patients, materials, and methods PatientsT-cell analyses in pediatric patients ...

show abstract

Section: Discussionmentioning

confidence: 99%

Defective T-helper cell function after T-cell–depleting therapy affecting naive and memory populations

Heitger

Winklehner

Obexer

et al. 2002

Blood

View full text Add to dashboard Cite

show abstract

“…For instance, CD69 is a C-type lectin (Lopez-Cabera et al, 1993) likely to contribute to adhesion and CD38 has been implicated in binding to endothelium (Xu et al, 1994). Furthermore, both CD69 and CD38 are involved in signal transduction and cell activation (Nakamura et al, 1989;Moretta et al, 1991;Tugores et al, 1992;Xu et al, 1994) and CD30, a member of the TNF receptor family, could modulate TIL effector function by interacting with the CD30 ligand in the tumour (Faustman et al, 1982).…”

Section: Tils Display Strong Activation-independent Binding To Endothmentioning

confidence: 99%

Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis

Adams

Yannelli²,

Newman³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Efficacy of cancer immunotherapy with cultured tumour-infiltrating lymphocytes (TlLs) depends upon infused TILs migrating into tumour-bearing tissue, in which they mediate an anti-tumour response. For TILs to enter a tumour, they must first bind to tumour endothelium, and this process depends on TILs expressing and regulating the function of relevant cell-surface receptors. We analysed the cell-surface phenotype and endothelial binding of TILs cultured from human melanoma and compared them with peripheral blood T cells and with allostimulated T cells cultured under similar conditions. Compared with peripheral blood T cells, TILs expressed high levels of five integrins, two other adhesion molecules, including the skin homing molecule CLA, and several activation markers and showed markedly enhanced integrin-mediated adhesion to a dermal microvascular endothelial cell line in vitro. Compared with the allostimulated T cells, TILs expressed higher levels of the cutaneous lymphocyte antigen (CLA), the adhesion molecule CD31 and the activation markers CD30 and CD69, but lower levels of several other adhesion and activation molecules. These phenotypic and functional properties of TILs should have complex effects on their migration in vivo. Expression of CLA, the skin homing receptor, may increase migration to melanoma (a skin cancer), whereas integrin activation may cause non-specific binding of TILs to other endothelium. Manipulation of the culture conditions in which TILs are expanded might result in a phenotype that is more conducive to selective tumour homing in vivo.

show abstract

“…In the case of T cells, the addition of anti-CD69 MAbs enhanced anti-CD3 and PMA-induced proliferation [23]–[25] through increased interleukin (IL)-2 and IL-2 receptor expression [26] [4]. However a later study using CD69 −/− mice argued against such a role, since Ag-specific T cell proliferation was unaffected in vivo [27].…”

Section: Introductionmentioning

confidence: 99%

CD69 Does Not Affect the Extent of T Cell Priming

et al. 2012

View full text Add to dashboard Cite

CD69 is rapidly upregulated on T cells upon activation. In this work we show that this is also the case for CD69 expression on dendritic cells (DC). Thus, the expression kinetics of CD69 on both cell types is reminiscent of the one of costimulatory molecules. Using mouse models of transgenic T cells, we aimed at evaluating the effect of monoclonal antibody (MAb)-based targeting and gene deficiency of CD69 expressed by either DC or T cells on the extent of antigen (Ag)-specific T cell priming, which could be the result of a putative role in costimulation as well as on DC maturation and Ag-processing and presentation. CD69 targeting or deficiency of DC did not affect their expression of costimulatory molecules nor their capacity to induce Ag-specific T cell proliferation in in vitro assays. Also, CD69 targeting or deficiency of transgenic T cells did not affect the minimal proliferative dose for different peptide agonists in vitro. In in vivo models of transgenic T cell transfer and local Ag injection, CD69 deficiency of transferred T cells did not affect the extent of the proliferative response in Ag-draining lymph nodes (LN). In agreement with these results, CD69 MAb targeting or gene deficiency of Vaccinia-virus (VACV) infected mice did not affect the endogenous formation of virus-specific CD8+ T cell populations at the peak of the primary immune response. Altogether our results argue against a possible role in costimulation or an effect on Ag processing and presentation for CD69.

show abstract

Human T cell activation. IV. T cell activation and proliferation via the early activation antigen EA 1.

Cited by 61 publications

References 22 publications

Defective T-helper cell function after T-cell–depleting therapy affecting naive and memory populations

Defective T-helper cell function after T-cell–depleting therapy affecting naive and memory populations

Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis

CD69 Does Not Affect the Extent of T Cell Priming

Contact Info

Product

Resources

About