Age-Related Persistent Clonal Expansions of CD28−Cells: Phenotypic and Molecular TCR Analysis Reveals both CD4+and CD4+CD8+Cells with Identical CDR3 Sequences

Colombatti, Alfonso; Doliana, Roberto; Schiappacassi, Mónica; Argentini, Carla; Tonutti, Elio; Feruglio, Cristina; Sala, Pierguido

doi:10.1006/clin.1998.4580

Cited by 52 publications

(39 citation statements)

References 41 publications

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“…Although DP T cells have never been described in human cancers, several investigators have reported their presence in small amount in circulating blood of healthy individuals. 23,24 Their frequency is considerably increased in some autoimmune [25][26][27][28] and infectious diseases. 29,30 DP T cells seem in fact to represent diverse subpopulations.…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Desfrançois

Derré

Corvaisier

et al. 2009

Intl Journal of Cancer

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Breast cancer remains a leading cause of cancer-related death within the female population. Immunotherapy is expected to provide additional therapeutic benefits but has met so far limited success. This may be due in part to the poor understanding of immune responses to breast cancer. Although CD4 1 and CD8 1 T lymphocytes infiltrate these tumors, the phenotype and functions of these cells remain ill defined. This study was designed to investigate further about these questions, taking advantage of multiparameter flow cytometry on lymphocytes derived from peripheral blood, solid tumors, metastatic lymph nodes and pleural effusions samples of patients with breast cancer. Results showed that, in addition to conventional CD4 1 and CD8 1 ab T cells, individual tumors and most pleural effusions contained significant fractions of unconventional double positive (DP) CD4 1 CD8 1 ab T cells. These DP T cells displayed the phenotype and cytotoxic potential of effector/memory activated CD8 1 T cells but differed essentially from these cells by a high production of IL-5 and IL-13. The increased frequency of DP T cells in advanced breast cancer and their high lytic potential and original cytokine profile suggest that this T-cell subset may play a specific role in the regulation of immune responses to human breast cancer. ' 2009 UICC

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Section: Discussionmentioning

confidence: 99%

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Desfrançois

Derré

Corvaisier

et al. 2009

Intl Journal of Cancer

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“…CD28 expression on CD8+ T cells did not differ significantly between groups, whereas the CD4+CD28− T-cell population showed a tendency to increase with worse functional status (data not shown). The double positive CD4 +CD8+ and CD4+NKG2D+ are two other subsets of T cells that have been related to aging (Pawelec 1995;Colombatti et al 1998;Alonso-Arias et al 2009). The proportion of CD4+CD8+ and CD4+NKG2D+ in the peripheral blood increased in elders with worse (Fig.…”

Section: Demographic and Hematologic Characteristics Of The Study Popmentioning

confidence: 99%

Relationship between functional ability in older people, immune system status, and intensity of response to CMV

Moro-García

Alonso-Arias

López-Vázquez

et al. 2011

AGE

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Shorter survival in the elderly has been associated with deterioration of the immune system and also with functional disability. To analyze the relationship between functional and immune impairment in older individuals, we studied 100 elderly who lived in a nursing home, were age matched, and grouped according to their functional status. We characterized cell subpopulations by flow cytometry, quantified TREC by RT-PCR, and measured the T-cell proliferation and activation response (IFN-γ by ELISPOT, CD69) against anti-CD3 and CMV. Specific antibody titers against influenza virus and CMV were determined by ELISA. Individuals with worse functional status had significantly higher levels of NK cells and fewer B cells. These poorly functioning elders also had a significantly lower proportion of CD4+ T cells, increased CD8+ T cells, and a decreased CD4/CD8 ratio. TREC levels in CD4+ T cells were significantly lower in individuals with a high disability. Lower TREC levels correlated with a lower frequency of naïve T-cell subpopulations (CD45RA+CCR7+) and higher percentages of effector cells (CD45RA−CCR7−). The functionally impaired group had lower anti-CD3 responses, but gradually increased responses against CMV. Similarly, the higher CMV titers were found in elderly with worse functional status. On the contrary, the functional response in vivo, and the titer of antibodies generated after vaccination against influenza virus, was higher in individuals with better performance status. In summary, we concluded that the functional decline of elderly individuals was clearly associated with the aging of their immune system, and the intensity of the response to CMV.

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“…TCR analysis of circulating CD4ϩCD8␣/␣ϩ DP T cells from healthy aging donors and from 1 patient with the acquired immunodeficiency syndrome revealed sharing of their TCR with CD4ϩ, but not with CD8ϩ, SP T cells (7,8), thus indicating that CD4ϩ SP T cells may acquire the CD8␣/␣ coreceptor in vivo. Similarly, activation of CD8␣/␤ϩ SP T cells can lead to the expression of low levels of CD4 (CD4 low CD8 high DP T cells) (9).…”

mentioning

confidence: 93%

Presence of CD4+CD8+ double‐positive T cells with very high interleukin‐4 production potential in lesional skin of patients with systemic sclerosis

Parel¹,

Aurrand-Lions²,

Scheja³

et al. 2007

Arthritis & Rheumatism

129

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Objective. Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin.Methods. We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo.Results. A distinct subset expressing both CD4 and CD8␣/␤ coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4؉ or CD8؉ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4؉ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo.Conclusion. The present findings show that T cells with the unusual CD4؉CD8؉ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts.

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Age-Related Persistent Clonal Expansions of CD28−Cells: Phenotypic and Molecular TCR Analysis Reveals both CD4+and CD4+CD8+Cells with Identical CDR3 Sequences

Cited by 52 publications

References 41 publications

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Relationship between functional ability in older people, immune system status, and intensity of response to CMV

Presence of CD4+CD8+ double‐positive T cells with very high interleukin‐4 production potential in lesional skin of patients with systemic sclerosis

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